Pub Date : 2024-04-20DOI: 10.1016/j.ceca.2024.102875
Wei-Yin Lin, Woo Young Chung, Shmuel Muallem
The core functions of the anoctamins are Cl− channel activity and phosphatidylserine (and perhaps other lipids) scrambling. These functions have been extensively studied in various tissues and cells. However, another function of the anoctamins that is less recognized and minimally explored is as tethers at membrane contact sites. This short review aims to examine evidence supporting the localization of the anoctamins at membrane contact sites, their tether properties, and their functions as tethers.
{"title":"The tether function of the anoctamins","authors":"Wei-Yin Lin, Woo Young Chung, Shmuel Muallem","doi":"10.1016/j.ceca.2024.102875","DOIUrl":"10.1016/j.ceca.2024.102875","url":null,"abstract":"<div><p>The core functions of the anoctamins are Cl<sup>−</sup> channel activity and phosphatidylserine (and perhaps other lipids) scrambling. These functions have been extensively studied in various tissues and cells. However, another function of the anoctamins that is less recognized and minimally explored is as tethers at membrane contact sites. This short review aims to examine evidence supporting the localization of the anoctamins at membrane contact sites, their tether properties, and their functions as tethers.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"121 ","pages":"Article 102875"},"PeriodicalIF":4.0,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140779286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-18DOI: 10.1016/j.ceca.2024.102889
Michele Dibattista , Simone Pifferi , Andres Hernandez-Clavijo , Anna Menini
Chemical senses allow animals to detect and discriminate a vast array of molecules. The olfactory system is responsible of the detection of small volatile molecules, while water dissolved molecules are detected by taste buds in the oral cavity. Moreover, many animals respond to signaling molecules such as pheromones and other semiochemicals through the vomeronasal organ. The peripheral organs dedicated to chemical detection convert chemical signals into perceivable information through the employment of diverse receptor types and the activation of multiple ion channels. Two ion channels, TMEM16B, also known as anoctamin2 (ANO2) and TMEM16A, or anoctamin1 (ANO1), encoding for Ca2+-activated Cl¯ channels, have been recently described playing critical roles in various cell types. This review aims to discuss the main properties of TMEM16A and TMEM16B-mediated currents and their physiological roles in chemical senses. In olfactory sensory neurons, TMEM16B contributes to amplify the odorant response, to modulate firing, response kinetics and adaptation. TMEM16A and TMEM16B shape the pattern of action potentials in vomeronasal sensory neurons increasing the interspike interval. In type I taste bud cells, TMEM16A is activated during paracrine signaling mediated by ATP. This review aims to shed light on the regulation of diverse signaling mechanisms and neuronal excitability mediated by Ca-activated Cl¯ channels, hinting at potential new roles for TMEM16A and TMEM16B in the chemical senses.
{"title":"The physiological roles of anoctamin2/TMEM16B and anoctamin1/TMEM16A in chemical senses","authors":"Michele Dibattista , Simone Pifferi , Andres Hernandez-Clavijo , Anna Menini","doi":"10.1016/j.ceca.2024.102889","DOIUrl":"https://doi.org/10.1016/j.ceca.2024.102889","url":null,"abstract":"<div><p>Chemical senses allow animals to detect and discriminate a vast array of molecules. The olfactory system is responsible of the detection of small volatile molecules, while water dissolved molecules are detected by taste buds in the oral cavity. Moreover, many animals respond to signaling molecules such as pheromones and other semiochemicals through the vomeronasal organ. The peripheral organs dedicated to chemical detection convert chemical signals into perceivable information through the employment of diverse receptor types and the activation of multiple ion channels. Two ion channels, TMEM16B, also known as anoctamin2 (ANO2) and TMEM16A, or anoctamin1 (ANO1), encoding for Ca<sup>2+</sup>-activated Cl¯ channels, have been recently described playing critical roles in various cell types. This review aims to discuss the main properties of TMEM16A and TMEM16B-mediated currents and their physiological roles in chemical senses. In olfactory sensory neurons, TMEM16B contributes to amplify the odorant response, to modulate firing, response kinetics and adaptation. TMEM16A and TMEM16B shape the pattern of action potentials in vomeronasal sensory neurons increasing the interspike interval. In type I taste bud cells, TMEM16A is activated during paracrine signaling mediated by ATP. This review aims to shed light on the regulation of diverse signaling mechanisms and neuronal excitability mediated by Ca-activated Cl¯ channels, hinting at potential new roles for TMEM16A and TMEM16B in the chemical senses.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"120 ","pages":"Article 102889"},"PeriodicalIF":4.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140649837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-17DOI: 10.1016/j.ceca.2024.102888
Karl Kunzelmann, Jiraporn Ousingsawat, Rainer Schreiber
Plasma membrane localized anoctamin 1, 2 and 6 (TMEM16A, B, F) have been examined in great detail with respect to structure and function, but much less is known about the other seven intracellular members of this exciting family of proteins. This is probably due to their limited accessibility in intracellular membranous compartments, such as the endoplasmic reticulum (ER) or endosomes. However, these so-called intracellular anoctamins are also found in the plasma membrane (PM) which adds to the confusion regarding their cellular role. Probably all intracellular anoctamins except of ANO8 operate as intracellular phospholipid (PL) scramblases, allowing for Ca2+-activated, passive transport of phospholipids like phosphatidylserine between both membrane leaflets. Probably all of them also conduct ions, which is probably part of their physiological function. In this brief overview, we summarize key findings on the biological functions of ANO3, 4, 5, 7, 8, 9 and 10 (TMEM16C, D, E, G, H, J, K) that are gradually coming to light. Compartmentalized regulation of intracellular Ca2+ signals, tethering of the ER to specific PM contact sites, and control of intracellular vesicular trafficking appear to be some of the functions of intracellular anoctamins, while loss of function and abnormal expression are the cause for various diseases.
{"title":"VSI: The anoctamins: Structure and function","authors":"Karl Kunzelmann, Jiraporn Ousingsawat, Rainer Schreiber","doi":"10.1016/j.ceca.2024.102888","DOIUrl":"https://doi.org/10.1016/j.ceca.2024.102888","url":null,"abstract":"<div><p>Plasma membrane localized anoctamin 1, 2 and 6 (TMEM16A, B, F) have been examined in great detail with respect to structure and function, but much less is known about the other seven intracellular members of this exciting family of proteins. This is probably due to their limited accessibility in intracellular membranous compartments, such as the endoplasmic reticulum (ER) or endosomes. However, these so-called intracellular anoctamins are also found in the plasma membrane (PM) which adds to the confusion regarding their cellular role. Probably all intracellular anoctamins except of ANO8 operate as intracellular phospholipid (PL) scramblases, allowing for Ca<sup>2+</sup>-activated, passive transport of phospholipids like phosphatidylserine between both membrane leaflets. Probably all of them also conduct ions, which is probably part of their physiological function. In this brief overview, we summarize key findings on the biological functions of ANO3, 4, 5, 7, 8, 9 and 10 (TMEM16C, D, E, G, H, J, K) that are gradually coming to light. Compartmentalized regulation of intracellular Ca<sup>2+</sup> signals, tethering of the ER to specific PM contact sites, and control of intracellular vesicular trafficking appear to be some of the functions of intracellular anoctamins, while loss of function and abnormal expression are the cause for various diseases.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"120 ","pages":"Article 102888"},"PeriodicalIF":4.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143416024000460/pdfft?md5=f58aed71b2a266518534bd100bcaf091&pid=1-s2.0-S0143416024000460-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140640944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-15DOI: 10.1016/j.ceca.2024.102885
Rainer Schreiber, Jiraporn Ousingsawat, Karl Kunzelmann
When activated by increase in intracellular Ca2+, anoctamins (TMEM16 proteins) operate as phospholipid scramblases and as ion channels. Anoctamin 1 (ANO1) is the Ca2+-activated epithelial anion-selective channel that is coexpressed together with the abundant scramblase ANO6 and additional intracellular anoctamins. In salivary and pancreatic glands, ANO1 is tightly packed in the apical membrane and secretes Cl−. Epithelia of airways and gut use cystic fibrosis transmembrane conductance regulator (CFTR) as an apical Cl− exit pathway while ANO1 supports Cl− secretion mainly by facilitating activation of luminal CFTR and basolateral K+ channels. Under healthy conditions ANO1 modulates intracellular Ca2+ signals by tethering the endoplasmic reticulum, and except of glands its direct secretory contribution as Cl− channel might be small, compared to CFTR. In the kidneys ANO1 supports proximal tubular acid secretion and protein reabsorption and probably helps to excrete HCO3−in the collecting duct epithelium. However, under pathological conditions as in polycystic kidney disease, ANO1 is strongly upregulated and may cause enhanced proliferation and cyst growth. Under pathological condition, ANO1 and ANO6 are upregulated and operate as secretory channel/phospholipid scramblases, partly by supporting Ca2+-dependent processes. Much less is known about the role of other epithelial anoctamins whose potential functions are discussed in this review.
{"title":"The anoctamins: Structure and function","authors":"Rainer Schreiber, Jiraporn Ousingsawat, Karl Kunzelmann","doi":"10.1016/j.ceca.2024.102885","DOIUrl":"https://doi.org/10.1016/j.ceca.2024.102885","url":null,"abstract":"<div><p>When activated by increase in intracellular Ca<sup>2+</sup>, anoctamins (TMEM16 proteins) operate as phospholipid scramblases and as ion channels. Anoctamin 1 (ANO1) is the Ca<sup>2+</sup>-activated epithelial anion-selective channel that is coexpressed together with the abundant scramblase ANO6 and additional intracellular anoctamins. In salivary and pancreatic glands, ANO1 is tightly packed in the apical membrane and secretes Cl<sup>−</sup>. Epithelia of airways and gut use cystic fibrosis transmembrane conductance regulator (CFTR) as an apical Cl<sup>−</sup> exit pathway while ANO1 supports Cl<sup>−</sup> secretion mainly by facilitating activation of luminal CFTR and basolateral <em>K</em><sup>+</sup> channels. Under healthy conditions ANO1 modulates intracellular Ca<sup>2+</sup> signals by tethering the endoplasmic reticulum, and except of glands its direct secretory contribution as Cl<sup>−</sup> channel might be small, compared to CFTR. In the kidneys ANO1 supports proximal tubular acid secretion and protein reabsorption and probably helps to excrete HCO<sub>3</sub><sup>−</sup>in the collecting duct epithelium. However, under pathological conditions as in polycystic kidney disease, ANO1 is strongly upregulated and may cause enhanced proliferation and cyst growth. Under pathological condition, ANO1 and ANO6 are upregulated and operate as secretory channel/phospholipid scramblases, partly by supporting Ca<sup>2+</sup>-dependent processes. Much less is known about the role of other epithelial anoctamins whose potential functions are discussed in this review.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"120 ","pages":"Article 102885"},"PeriodicalIF":4.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143416024000435/pdfft?md5=6adf751f62121e312218f7d0a3c538d0&pid=1-s2.0-S0143416024000435-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140620607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-08DOI: 10.1016/j.ceca.2024.102882
Shefeeq M. Theparambil , Gulnaz Begum , Christine R. Rose
Strict homeostatic control of pH in both intra- and extracellular compartments of the brain is fundamentally important, primarily due to the profound impact of free protons ([H+]) on neuronal activity and overall brain function. Astrocytes, crucial players in the homeostasis of various ions in the brain, actively regulate their intracellular [H+] (pHi) through multiple membrane transporters and carbonic anhydrases. The activation of astroglial pHi regulating mechanisms also leads to corresponding alterations in the acid-base status of the extracellular fluid. Notably, astrocyte pH regulators are modulated by various neuronal signals, suggesting their pivotal role in regulating brain acid-base balance in both health and disease. This review presents the mechanisms involved in pH regulation in astrocytes and discusses their potential impact on extracellular pH under physiological conditions and in brain disorders. Targeting astrocytic pH regulatory mechanisms represents a promising therapeutic approach for modulating brain acid-base balance in diseases, offering a potential critical contribution to neuroprotection.
{"title":"pH regulating mechanisms of astrocytes: A critical component in physiology and disease of the brain","authors":"Shefeeq M. Theparambil , Gulnaz Begum , Christine R. Rose","doi":"10.1016/j.ceca.2024.102882","DOIUrl":"https://doi.org/10.1016/j.ceca.2024.102882","url":null,"abstract":"<div><p>Strict homeostatic control of pH in both intra- and extracellular compartments of the brain is fundamentally important, primarily due to the profound impact of free protons ([<em>H</em><sup>+</sup>]) on neuronal activity and overall brain function. Astrocytes, crucial players in the homeostasis of various ions in the brain, actively regulate their intracellular [<em>H</em><sup>+</sup>] (pH<sub>i</sub>) through multiple membrane transporters and carbonic anhydrases. The activation of astroglial pH<sub>i</sub> regulating mechanisms also leads to corresponding alterations in the acid-base status of the extracellular fluid. Notably, astrocyte pH regulators are modulated by various neuronal signals, suggesting their pivotal role in regulating brain acid-base balance in both health and disease. This review presents the mechanisms involved in pH regulation in astrocytes and discusses their potential impact on extracellular pH under physiological conditions and in brain disorders. Targeting astrocytic pH regulatory mechanisms represents a promising therapeutic approach for modulating brain acid-base balance in diseases, offering a potential critical contribution to neuroprotection.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"120 ","pages":"Article 102882"},"PeriodicalIF":4.0,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S014341602400040X/pdfft?md5=03f3d9286d0f6ca600257cdc4408fefb&pid=1-s2.0-S014341602400040X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140555192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-08DOI: 10.1016/j.ceca.2024.102883
Charlotte Suckert , Carolin Zosel , Michael Schaefer
The basal and glucose-induced insulin secretion from pancreatic beta cells is a tightly regulated process that is triggered in a Ca2+-dependent fashion and further positively modulated by substances that raise intracellular levels of adenosine 3′,5′-cyclic monophosphate (cAMP) or by certain antidiabetic drugs. In a previous study, we have temporally resolved the subplasmalemmal [Ca2+]i dynamics in beta cells that are characterized by trains of sharply delimited spikes, reaching peak values up to 5 µM. Applying total internal reflection fluorescence (TIRF) microscopy and synaptopHluorin to visualize fusion events of individual granules, we found that several fusion events can coincide within 50 to 150 ms. To test whether subplasmalemmal [Ca2+]i microdomains around single or clustered Ca2+ channels may cause a synchronized release of insulin-containing vesicles, we applied simultaneous dual-color TIRF microscopy and monitored Ca2+ fluctuations and exocytotic events in INS-1 cells at high frame rates. The results indicate that fusions can be triggered by subplasmalemmal Ca2+ spiking. This, however, does account for a minority of fusion events. About 90 %-95 % of fusion events either happen between Ca2+ spikes or incidentally overlap with subplasmalemmal Ca2+ spikes. We conclude that only a fraction of exocytotic events in glucose-induced and tolbutamide- or forskolin-enhanced insulin release from INS-1 cells is tightly coupled to Ca2+ microdomains around voltage-gated Ca2+ channels.
{"title":"Simultaneous TIRF imaging of subplasmalemmal Ca2+ dynamics and granule fusions in insulin-secreting INS-1 cells reveals coexistent synchronized and asynchronous release","authors":"Charlotte Suckert , Carolin Zosel , Michael Schaefer","doi":"10.1016/j.ceca.2024.102883","DOIUrl":"https://doi.org/10.1016/j.ceca.2024.102883","url":null,"abstract":"<div><p>The basal and glucose-induced insulin secretion from pancreatic beta cells is a tightly regulated process that is triggered in a Ca<sup>2+</sup>-dependent fashion and further positively modulated by substances that raise intracellular levels of adenosine 3′,5′-cyclic monophosphate (cAMP) or by certain antidiabetic drugs. In a previous study, we have temporally resolved the subplasmalemmal [Ca<sup>2+</sup>]<sub>i</sub> dynamics in beta cells that are characterized by trains of sharply delimited spikes, reaching peak values up to 5 µM. Applying total internal reflection fluorescence (TIRF) microscopy and synaptopHluorin to visualize fusion events of individual granules, we found that several fusion events can coincide within 50 to 150 ms. To test whether subplasmalemmal [Ca<sup>2+</sup>]<sub>i</sub> microdomains around single or clustered Ca<sup>2+</sup> channels may cause a synchronized release of insulin-containing vesicles, we applied simultaneous dual-color TIRF microscopy and monitored Ca<sup>2+</sup> fluctuations and exocytotic events in INS-1 cells at high frame rates. The results indicate that fusions can be triggered by subplasmalemmal Ca<sup>2+</sup> spiking. This, however, does account for a minority of fusion events. About 90 %-95 % of fusion events either happen between Ca<sup>2+</sup> spikes or incidentally overlap with subplasmalemmal Ca<sup>2+</sup> spikes. We conclude that only a fraction of exocytotic events in glucose-induced and tolbutamide- or forskolin-enhanced insulin release from INS-1 cells is tightly coupled to Ca<sup>2+</sup> microdomains around voltage-gated Ca<sup>2+</sup> channels.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"120 ","pages":"Article 102883"},"PeriodicalIF":4.0,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143416024000411/pdfft?md5=85c9b28c7c9d3d4d9253198eaf4bcd8d&pid=1-s2.0-S0143416024000411-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140621812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-08DOI: 10.1016/j.ceca.2024.102887
Mai Makino , Shuhei Nakamura
{"title":"A novel probe to monitor lysosome-mitochondria contact sites opens up a new path to study neurodegenerative diseases","authors":"Mai Makino , Shuhei Nakamura","doi":"10.1016/j.ceca.2024.102887","DOIUrl":"https://doi.org/10.1016/j.ceca.2024.102887","url":null,"abstract":"","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"120 ","pages":"Article 102887"},"PeriodicalIF":4.0,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140536794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-06DOI: 10.1016/j.ceca.2024.102886
Zhengwei Luo , Xinyang Zhang , Andrea Fleig , Daniel Romo , Kenneth G. Hull , F. David Horgen , Hong-Shuo Sun , Zhong-Ping Feng
Neurodevelopment, a complex and highly regulated process, plays a foundational role in shaping the structure and function of the nervous system. The transient receptor potential melastatin 7 (TRPM7), a divalent cation channel with an α-kinase domain, mediates a wide range of cellular functions, including proliferation, migration, cell adhesion, and survival, all of which are essential processes in neurodevelopment. The global knockout of either TRPM7 or TRPM7-kinase is embryonically lethal, highlighting the crucial role of TRPM7 in development in vivo. Subsequent research further revealed that TRPM7 is indeed involved in various key processes throughout neurodevelopment, from maintaining pluripotency during embryogenesis to regulating gastrulation, neural tube closure, axonal outgrowth, synaptic density, and learning and memory. Moreover, a discrepancy in TRPM7 expression and/or function has been associated with neuropathological conditions, including ischemic stroke, Alzheimer's disease, and Parkinson's disease. Understanding the mechanisms of proper neurodevelopment may provide us with the knowledge required to develop therapeutic interventions that can overcome the challenges of regeneration in CNS injuries and neurodegenerative diseases. Considering that ion channels are the third-largest class targeted for drug development, TRPM7′s dual roles in development and degeneration emphasize its therapeutic potential. This review provides a comprehensive overview of the current literature on TRPM7 in various aspects of neurodevelopment. It also discusses the links between neurodevelopment and neurodegeneration, and highlights TRPM7 as a potential therapeutic target for neurodegenerative disorders, with a focus on repair and regeneration.
{"title":"TRPM7 in neurodevelopment and therapeutic prospects for neurodegenerative disease","authors":"Zhengwei Luo , Xinyang Zhang , Andrea Fleig , Daniel Romo , Kenneth G. Hull , F. David Horgen , Hong-Shuo Sun , Zhong-Ping Feng","doi":"10.1016/j.ceca.2024.102886","DOIUrl":"https://doi.org/10.1016/j.ceca.2024.102886","url":null,"abstract":"<div><p>Neurodevelopment, a complex and highly regulated process, plays a foundational role in shaping the structure and function of the nervous system. The transient receptor potential melastatin 7 (TRPM7), a divalent cation channel with an α-kinase domain, mediates a wide range of cellular functions, including proliferation, migration, cell adhesion, and survival, all of which are essential processes in neurodevelopment. The global knockout of either TRPM7 or TRPM7-kinase is embryonically lethal, highlighting the crucial role of TRPM7 in development <em>in vivo</em>. Subsequent research further revealed that TRPM7 is indeed involved in various key processes throughout neurodevelopment, from maintaining pluripotency during embryogenesis to regulating gastrulation, neural tube closure, axonal outgrowth, synaptic density, and learning and memory. Moreover, a discrepancy in TRPM7 expression and/or function has been associated with neuropathological conditions, including ischemic stroke, Alzheimer's disease, and Parkinson's disease. Understanding the mechanisms of proper neurodevelopment may provide us with the knowledge required to develop therapeutic interventions that can overcome the challenges of regeneration in CNS injuries and neurodegenerative diseases. Considering that ion channels are the third-largest class targeted for drug development, TRPM7′s dual roles in development and degeneration emphasize its therapeutic potential. This review provides a comprehensive overview of the current literature on TRPM7 in various aspects of neurodevelopment. It also discusses the links between neurodevelopment and neurodegeneration, and highlights TRPM7 as a potential therapeutic target for neurodegenerative disorders, with a focus on repair and regeneration.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"120 ","pages":"Article 102886"},"PeriodicalIF":4.0,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140558195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-02DOI: 10.1016/j.ceca.2024.102884
Jami L. Saloman , Ariel Y. Epouhe , Catherine F. Ruff , Kathryn M. Albers
Pancreatic and duodenal homeobox 1 (PDX1) is a transcription factor required for the development and differentiation of the pancreas. Previous studies indicated that PDX1 expression was restricted to the gastrointestinal tract. Using a cre-dependent reporter, we observed PDX1-dependent expression of tdtomato (PDX1-tom) in a subpopulation of sensory nerves. Many of these PDX1-tom afferents expressed the neurofilament 200 protein and projected to the skin. Tdtomato-labeled terminals were associated with hair follicles in the form of longitudinal and circumferential lanceolate endings suggesting a role in tactile and proprioceptive perception. To begin to examine the functional significance of PDX1 in afferents, we used Fura-2 imaging to examine calcium (Ca2+) handling under naïve and nerve injury conditions. Neuropathic injury is associated with increased intracellular Ca2+ signaling that in part results from dysregulation of the sarco/endoplasmic reticulum calcium transport ATPase (SERCA). Here we demonstrate that under naïve conditions, PDX1 regulates expression of the SERCA2B isoform in sensory neurons. In response to infraorbital nerve injury, a significant reduction of PDX1 and SERCA2B expression and dysregulation of Ca2+ handling occurs in PDX1-tom trigeminal ganglia neurons. The identification of PDX1 expression in the somatosensory system and its regulation of SERCA2B and Ca2+ handling provide a new mechanism to explain pathological changes in primary afferents that may contribute to pain associated with nerve injury.
{"title":"PDX1, a transcription factor essential for organ differentiation, regulates SERCA-dependent Ca2+ homeostasis in sensory neurons","authors":"Jami L. Saloman , Ariel Y. Epouhe , Catherine F. Ruff , Kathryn M. Albers","doi":"10.1016/j.ceca.2024.102884","DOIUrl":"https://doi.org/10.1016/j.ceca.2024.102884","url":null,"abstract":"<div><p>Pancreatic and duodenal homeobox 1 (PDX1) is a transcription factor required for the development and differentiation of the pancreas. Previous studies indicated that PDX1 expression was restricted to the gastrointestinal tract. Using a cre-dependent reporter, we observed PDX1-dependent expression of tdtomato (PDX1-tom) in a subpopulation of sensory nerves. Many of these PDX1-tom afferents expressed the neurofilament 200 protein and projected to the skin. Tdtomato-labeled terminals were associated with hair follicles in the form of longitudinal and circumferential lanceolate endings suggesting a role in tactile and proprioceptive perception. To begin to examine the functional significance of PDX1 in afferents, we used Fura-2 imaging to examine calcium (Ca<sup>2+</sup>) handling under naïve and nerve injury conditions. Neuropathic injury is associated with increased intracellular Ca<sup>2+</sup> signaling that in part results from dysregulation of the sarco/endoplasmic reticulum calcium transport ATPase (SERCA). Here we demonstrate that under naïve conditions, PDX1 regulates expression of the SERCA2B isoform in sensory neurons. In response to infraorbital nerve injury, a significant reduction of PDX1 and SERCA2B expression and dysregulation of Ca<sup>2+</sup> handling occurs in PDX1-tom trigeminal ganglia neurons. The identification of PDX1 expression in the somatosensory system and its regulation of SERCA2B and Ca<sup>2+</sup> handling provide a new mechanism to explain pathological changes in primary afferents that may contribute to pain associated with nerve injury.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"120 ","pages":"Article 102884"},"PeriodicalIF":4.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140341236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-20DOI: 10.1016/j.ceca.2024.102873
Karla M. Márquez-Nogueras, Elisa Bovo, Jacy E. Neczypor, Quan Cao, Aleksey V. Zima, Ivana Y. Kuo
Calcium signaling is a critical process required for cellular mechanisms such as cardiomyocyte contraction. The inability of the cell to properly activate or regulate calcium signaling can lead to contractile dysfunction. In isolated cardiomyocytes, calcium signaling has been primarily studied using calcium fluorescent dyes, however these dyes have limited applicability to whole organs. Here, we crossed the Salsa6f mouse which expresses a genetically encoded ratiometric cytosolic calcium indicator with a cardiomyocyte specific inducible cre to temporally-induce expression and studied cytosolic calcium transients in isolated cardiomyocytes and modified Langendorff heart preparations. Isolated cardiomyocytes expressing Salsa6f or Fluo-4AM loaded were compared. We also crossed the Salsa6f mouse with a floxed Polycystin 2 (PC2) mouse to test the feasibility of using the Salsa6f mouse to measure calcium transients in PC2 heterozygous or homozygous knock out mice. Although there are caveats in the applicability of the Salsa6f mouse, there are clear advantages to using the Salsa6f mouse to measure whole heart calcium signals.
{"title":"Utilization of the genetically encoded calcium indicator Salsa6F in cardiac applications","authors":"Karla M. Márquez-Nogueras, Elisa Bovo, Jacy E. Neczypor, Quan Cao, Aleksey V. Zima, Ivana Y. Kuo","doi":"10.1016/j.ceca.2024.102873","DOIUrl":"10.1016/j.ceca.2024.102873","url":null,"abstract":"<div><p>Calcium signaling is a critical process required for cellular mechanisms such as cardiomyocyte contraction. The inability of the cell to properly activate or regulate calcium signaling can lead to contractile dysfunction. In isolated cardiomyocytes, calcium signaling has been primarily studied using calcium fluorescent dyes, however these dyes have limited applicability to whole organs. Here, we crossed the Salsa6f mouse which expresses a genetically encoded ratiometric cytosolic calcium indicator with a cardiomyocyte specific inducible cre to temporally-induce expression and studied cytosolic calcium transients in isolated cardiomyocytes and modified Langendorff heart preparations. Isolated cardiomyocytes expressing Salsa6f or Fluo-4AM loaded were compared. We also crossed the Salsa6f mouse with a floxed Polycystin 2 (PC2) mouse to test the feasibility of using the Salsa6f mouse to measure calcium transients in PC2 heterozygous or homozygous knock out mice. Although there are caveats in the applicability of the Salsa6f mouse, there are clear advantages to using the Salsa6f mouse to measure whole heart calcium signals.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"119 ","pages":"Article 102873"},"PeriodicalIF":4.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140272508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}