Pub Date : 2023-08-06eCollection Date: 2023-01-01DOI: 10.1177/25152564231189064
Diego Huet, Silvia N J Moreno
Apicomplexan parasites are a group of protists that cause disease in humans and include pathogens like Plasmodium spp., the causative agent of malaria, and Toxoplasma gondii, the etiological agent of toxoplasmosis and one of the most ubiquitous human parasites in the world. Membrane contact sites (MCSs) are widespread structures within eukaryotic cells but their characterization in apicomplexan parasites is only in its very beginnings. Basic biological features of the T. gondii parasitic cycle support numerous organellar interactions, including the transfer of Ca2+ and metabolites between different compartments. In T. gondii, Ca2+ signals precede a series of interrelated molecular processes occurring in a coordinated manner that culminate in the stimulation of key steps of the parasite life cycle. Calcium transfer from the endoplasmic reticulum to other organelles via MCSs would explain the precision, speed, and efficiency that is needed during the lytic cycle of T. gondii. In this short review, we discuss the implications of these structures in cellular signaling, with an emphasis on their potential role in Ca2+ signaling.
{"title":"Interorganellar Communication Through Membrane Contact Sites in <i>Toxoplasma Gondii</i>.","authors":"Diego Huet, Silvia N J Moreno","doi":"10.1177/25152564231189064","DOIUrl":"10.1177/25152564231189064","url":null,"abstract":"<p><p>Apicomplexan parasites are a group of protists that cause disease in humans and include pathogens like <i>Plasmodium spp</i>., the causative agent of malaria, and <i>Toxoplasma gondii</i>, the etiological agent of toxoplasmosis and one of the most ubiquitous human parasites in the world. Membrane contact sites (MCSs) are widespread structures within eukaryotic cells but their characterization in apicomplexan parasites is only in its very beginnings. Basic biological features of the <i>T. gondii</i> parasitic cycle support numerous organellar interactions, including the transfer of Ca<sup>2+</sup> and metabolites between different compartments. In <i>T. gondii</i>, Ca<sup>2+</sup> signals precede a series of interrelated molecular processes occurring in a coordinated manner that culminate in the stimulation of key steps of the parasite life cycle. Calcium transfer from the endoplasmic reticulum to other organelles via MCSs would explain the precision, speed, and efficiency that is needed during the lytic cycle of <i>T. gondii</i>. In this short review, we discuss the implications of these structures in cellular signaling, with an emphasis on their potential role in Ca<sup>2+</sup> signaling.</p>","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"6 ","pages":"25152564231189064"},"PeriodicalIF":0.0,"publicationDate":"2023-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ab/fd/10.1177_25152564231189064.PMC10408353.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10305082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-12eCollection Date: 2023-01-01DOI: 10.1177/25152564231185931
Sujeet Kumar, Natividad Ruiz
In eukaryotic cells, nonvesicular lipid transport between organelles is mediated by lipid-transfer proteins. Recently, a new class of these lipid transporters has been described to facilitate the bulk of inter-organelle lipid transport at contact sites by forming bridge-like structures with a hydrophobic groove through which lipids travel. Because their predicted structure is composed of repeating β-groove (RBG) domains, they have been named the RBG protein superfamily. Early studies on RBG proteins VPS13 and ATG2 recognized the resemblance of their predicted structures to that of the bacterial Lpt system, which transports newly synthesized lipopolysaccharides (LPS) between the inner and the outer membranes (IMs and OMs) of Gram-negative bacteria. In these didermic bacteria, the IMs and OMs are separated by an aqueous periplasmic compartment that is traversed by a bridge-like structure built with β-jelly roll domains from several Lpt proteins that provides a hydrophobic groove for LPS molecules to travel across the periplasm. Despite structural and functional similarities between RBG proteins and the Lpt system, the bacterial AsmA-like protein family has recently emerged as the likely ancestor of RBG proteins and long sought-after transporters that facilitate the transfer of phospholipids from the IM to the OM. Here, we review our current understanding of the structure and function of bacterial AsmA-like proteins, mainly focusing on recent studies that have led to the proposal that AsmA-like proteins mediate the bulk of phospholipid transfer between the IMs and OMs.
在真核细胞中,细胞器之间的非囊泡脂质运输是由脂质转移蛋白介导的。最近,一类新的脂质转运蛋白被描述出来,它们通过形成具有疏水槽的桥状结构,使脂质通过疏水槽,从而促进了大部分细胞器间脂质在接触部位的转运。由于它们的预测结构由重复的 β 沟(RBG)结构域组成,因此被命名为 RBG 蛋白超家族。对 RBG 蛋白 VPS13 和 ATG2 的早期研究发现,它们的预测结构与细菌的 Lpt 系统相似,后者在革兰氏阴性细菌的内膜和外膜(IMs 和 OMs)之间运输新合成的脂多糖(LPS)。在这些真菌中,内膜和外膜被一个含水的周质区隔开,周质区由一个桥状结构穿过,该结构由多个 Lpt 蛋白的β-果冻卷结构域构建而成,为 LPS 分子穿过周质提供了一个疏水槽。尽管 RBG 蛋白和 Lpt 系统在结构和功能上有相似之处,但最近出现的细菌 AsmA 样蛋白家族可能是 RBG 蛋白的祖先,也是人们长期寻找的促进磷脂从 IM 转移到 OM 的转运体。在此,我们回顾了目前我们对细菌 AsmA 样蛋白的结构和功能的理解,主要侧重于最近的研究,这些研究提出 AsmA 样蛋白介导了大部分磷脂在 IM 和 OM 之间的转移。
{"title":"Bacterial AsmA-Like Proteins: Bridging the Gap in Intermembrane Phospholipid Transport.","authors":"Sujeet Kumar, Natividad Ruiz","doi":"10.1177/25152564231185931","DOIUrl":"10.1177/25152564231185931","url":null,"abstract":"<p><p>In eukaryotic cells, nonvesicular lipid transport between organelles is mediated by lipid-transfer proteins. Recently, a new class of these lipid transporters has been described to facilitate the bulk of inter-organelle lipid transport at contact sites by forming bridge-like structures with a hydrophobic groove through which lipids travel. Because their predicted structure is composed of repeating β-groove (RBG) domains, they have been named the RBG protein superfamily. Early studies on RBG proteins VPS13 and ATG2 recognized the resemblance of their predicted structures to that of the bacterial Lpt system, which transports newly synthesized lipopolysaccharides (LPS) between the inner and the outer membranes (IMs and OMs) of Gram-negative bacteria. In these didermic bacteria, the IMs and OMs are separated by an aqueous periplasmic compartment that is traversed by a bridge-like structure built with β-jelly roll domains from several Lpt proteins that provides a hydrophobic groove for LPS molecules to travel across the periplasm. Despite structural and functional similarities between RBG proteins and the Lpt system, the bacterial AsmA-like protein family has recently emerged as the likely ancestor of RBG proteins and long sought-after transporters that facilitate the transfer of phospholipids from the IM to the OM. Here, we review our current understanding of the structure and function of bacterial AsmA-like proteins, mainly focusing on recent studies that have led to the proposal that AsmA-like proteins mediate the bulk of phospholipid transfer between the IMs and OMs.</p>","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"6 ","pages":"25152564231185931"},"PeriodicalIF":0.0,"publicationDate":"2023-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/86/ae/10.1177_25152564231185931.PMC10345924.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10353105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-12eCollection Date: 2023-01-01DOI: 10.1177/25152564231186489
Taruna Pandey, Jianxiu Zhang, Bingying Wang, Dengke K Ma
In eukaryotic cells, lipid transfer can occur at membrane contact sites (MCS) to facilitate the exchange of various lipids between two adjacent cellular organelle membranes. Lipid transfer proteins (LTPs), including shuttle LTP or bridge-like LTP (BLTP), transport lipids at MCS and are critical for diverse cellular processes, including lipid metabolism, membrane trafficking, and cell signaling. BLTPs (BLTP1-5, including the ATG2 and VPS13 family proteins) contain lipid-accommodating hydrophobic repeating β-groove (RBG) domains that allow the bulk transfer of lipids through MCS. Compared with vesicular lipid transfer and shuttle LTP, BLTPs have been only recently identified. Their functions and regulatory mechanisms are currently being unraveled in various model organisms and by diverse approaches. In this review, we summarize the genetics, structural features, and biological functions of BLTP in the genetically tractable model organism C. elegans. We discuss our recent studies and findings on C. elegans LPD-3, a prototypical megaprotein ortholog of BLTP1, with identified lipid transfer functions that are evolutionarily conserved in multicellular organisms and in human cells. We also highlight areas for future research of BLTP using C. elegans and complementary model systems and approaches. Given the emerging links of BLTP to several human diseases, including Parkinson's disease and Alkuraya-Kučinskas syndrome, discovering evolutionarily conserved roles of BLTPs and their mechanisms of regulation and action should contribute to new advances in basic cell biology and potential therapeutic development for related human disorders.
{"title":"Bridge-Like Lipid Transfer Proteins (BLTPs) in <i>C. elegans</i>: From Genetics to Structures and Functions.","authors":"Taruna Pandey, Jianxiu Zhang, Bingying Wang, Dengke K Ma","doi":"10.1177/25152564231186489","DOIUrl":"10.1177/25152564231186489","url":null,"abstract":"<p><p>In eukaryotic cells, lipid transfer can occur at membrane contact sites (MCS) to facilitate the exchange of various lipids between two adjacent cellular organelle membranes. Lipid transfer proteins (LTPs), including shuttle LTP or bridge-like LTP (BLTP), transport lipids at MCS and are critical for diverse cellular processes, including lipid metabolism, membrane trafficking, and cell signaling. BLTPs (BLTP1-5, including the ATG2 and VPS13 family proteins) contain lipid-accommodating hydrophobic repeating β-groove (RBG) domains that allow the bulk transfer of lipids through MCS. Compared with vesicular lipid transfer and shuttle LTP, BLTPs have been only recently identified. Their functions and regulatory mechanisms are currently being unraveled in various model organisms and by diverse approaches. In this review, we summarize the genetics, structural features, and biological functions of BLTP in the genetically tractable model organism <i>C. elegans</i>. We discuss our recent studies and findings on <i>C. elegans</i> LPD-3, a prototypical megaprotein ortholog of BLTP1, with identified lipid transfer functions that are evolutionarily conserved in multicellular organisms and in human cells. We also highlight areas for future research of BLTP using <i>C. elegans</i> and complementary model systems and approaches. Given the emerging links of BLTP to several human diseases, including Parkinson's disease and Alkuraya-Kučinskas syndrome, discovering evolutionarily conserved roles of BLTPs and their mechanisms of regulation and action should contribute to new advances in basic cell biology and potential therapeutic development for related human disorders.</p>","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"6 ","pages":"25152564231186489"},"PeriodicalIF":0.0,"publicationDate":"2023-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f0/3c/10.1177_25152564231186489.PMC10345909.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10353104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-22eCollection Date: 2023-01-01DOI: 10.1177/25152564231181020
Peace Atakpa-Adaji, Adelina Ivanova
Membrane contact sites (MCS) circumvent the topological constraints of functional coupling between different membrane-bound organelles by providing a means of communication and exchange of materials. One of the most characterised contact sites in the cell is that between the endoplasmic reticulum and the mitochondrial (ERMCS) whose function is to couple cellular Ca2+ homeostasis and mitochondrial function. Inositol 1,4,5-trisphosphate receptors (IP3Rs) on the ER, glucose-regulated protein 75 (GRP 75) and voltage-dependent anion channel 1 (VDAC1) on the outer mitochondrial membrane are the canonical component of the Ca2+ transfer unit at ERMCS. These are often reported to form a Ca2+ funnel that fuels the mitochondrial low-affinity Ca2+ uptake system. We assess the available evidence on the IP3R subtype selectivity at the ERMCS and consider if IP3Rs have other roles at the ERMCS beyond providing Ca2+. Growing evidence suggests that all three IP3R subtypes can localise and regulate Ca2+ signalling at ERMCS. Furthermore, IP3Rs may be structurally important for assembly of the ERMCS in addition to their role in providing Ca2+ at these sites. Evidence that various binding partners regulate the assembly and Ca2+ transfer at ERMCS populated by IP3R-GRP75-VDAC1, suggesting that cells have evolved mechanisms that stabilise these junctions forming a Ca2+ microdomain that is required to fuel mitochondrial Ca2+ uptake.
{"title":"IP<sub>3</sub>R at ER-Mitochondrial Contact Sites: Beyond the IP<sub>3</sub>R-GRP75-VDAC1 Ca<sup>2+</sup> Funnel.","authors":"Peace Atakpa-Adaji, Adelina Ivanova","doi":"10.1177/25152564231181020","DOIUrl":"10.1177/25152564231181020","url":null,"abstract":"<p><p>Membrane contact sites (MCS) circumvent the topological constraints of functional coupling between different membrane-bound organelles by providing a means of communication and exchange of materials. One of the most characterised contact sites in the cell is that between the endoplasmic reticulum and the mitochondrial (ERMCS) whose function is to couple cellular Ca<sup>2+</sup> homeostasis and mitochondrial function. Inositol 1,4,5-trisphosphate receptors (IP<sub>3</sub>Rs) on the ER, glucose-regulated protein 75 (GRP 75) and voltage-dependent anion channel 1 (VDAC1) on the outer mitochondrial membrane are the canonical component of the Ca<sup>2+</sup> transfer unit at ERMCS. These are often reported to form a Ca<sup>2+</sup> funnel that fuels the mitochondrial low-affinity Ca<sup>2+</sup> uptake system. We assess the available evidence on the IP<sub>3</sub>R subtype selectivity at the ERMCS and consider if IP<sub>3</sub>Rs have other roles at the ERMCS beyond providing Ca<sup>2+</sup>. Growing evidence suggests that all three IP<sub>3</sub>R subtypes can localise and regulate Ca<sup>2+</sup> signalling at ERMCS. Furthermore, IP<sub>3</sub>Rs may be structurally important for assembly of the ERMCS in addition to their role in providing Ca<sup>2+</sup> at these sites. Evidence that various binding partners regulate the assembly and Ca<sup>2+</sup> transfer at ERMCS populated by IP<sub>3</sub>R-GRP75-VDAC1, suggesting that cells have evolved mechanisms that stabilise these junctions forming a Ca<sup>2+</sup> microdomain that is required to fuel mitochondrial Ca<sup>2+</sup> uptake.</p>","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"6 ","pages":"25152564231181020"},"PeriodicalIF":0.0,"publicationDate":"2023-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10328019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10352546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-09eCollection Date: 2023-01-01DOI: 10.1177/25152564231162495
Cristina Capitanio, Anna Bieber, Florian Wilfling
During macroautophagy, phagophores establish multiple membrane contact sites (MCSs) with other organelles that are pivotal for proper phagophore assembly and growth. In S. cerevisiae, phagophore contacts have been observed with the vacuole, the ER, and lipid droplets. In situ imaging studies have greatly advanced our understanding of the structure and function of these sites. Here, we discuss how in situ structural methods like cryo-CLEM can give unprecedented insights into MCSs, and how they help to elucidate the structural arrangements of MCSs within cells. We further summarize the current knowledge of the contact sites in autophagy, focusing on autophagosome biogenesis in the model organism S. cerevisiae.
{"title":"How Membrane Contact Sites Shape the Phagophore.","authors":"Cristina Capitanio, Anna Bieber, Florian Wilfling","doi":"10.1177/25152564231162495","DOIUrl":"10.1177/25152564231162495","url":null,"abstract":"<p><p>During macroautophagy, phagophores establish multiple membrane contact sites (MCSs) with other organelles that are pivotal for proper phagophore assembly and growth. In <i>S. cerevisiae</i>, phagophore contacts have been observed with the vacuole, the ER, and lipid droplets. In situ imaging studies have greatly advanced our understanding of the structure and function of these sites. Here, we discuss how in situ structural methods like cryo-CLEM can give unprecedented insights into MCSs, and how they help to elucidate the structural arrangements of MCSs within cells. We further summarize the current knowledge of the contact sites in autophagy, focusing on autophagosome biogenesis in the model organism <i>S. cerevisiae</i>.</p>","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"6 ","pages":"25152564231162495"},"PeriodicalIF":0.0,"publicationDate":"2023-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10243513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10298545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-23eCollection Date: 2023-01-01DOI: 10.1177/25152564231156994
Kevin Peikert, Adrian Danek
In 2020, the pandemic interrupted the series of biannual International Neuroacanthocytosis Meetings that brought together clinicians, scientists, and patient groups to share research into a small group of devastating genetic diseases that combine both acanthocytosis (deformed red blood cells) and neurodegeneration with movement disorders. This Meeting Report describes talks at the 5th VPS13 Forum in January 2022, one of a series of online meetings held to fill the gap. The meeting addressed the basic biology of two key proteins implicated in chorea-acanthocytosis (mutations in VPS13A) and McLeod syndrome (mutations in XK). In a remarkable confluence of ideas, the speakers described different aspects of a single functional unit that comprises of VPS13A and XK proteins working together. Conditions caused by VPS13 (A-D) gene family mutations and related genes, such as XK, previously footnote knowledge, seem to turn central for a novel disease paradigm: bulk lipid transfer disorders.
{"title":"VPS13 Forum Proceedings: XK, XK-Related and VPS13 Proteins in Membrane Lipid Dynamics.","authors":"Kevin Peikert, Adrian Danek","doi":"10.1177/25152564231156994","DOIUrl":"10.1177/25152564231156994","url":null,"abstract":"<p><p>In 2020, the pandemic interrupted the series of biannual International Neuroacanthocytosis Meetings that brought together clinicians, scientists, and patient groups to share research into a small group of devastating genetic diseases that combine both acanthocytosis (deformed red blood cells) and neurodegeneration with movement disorders. This Meeting Report describes talks at the 5th <i>VPS13 Forum</i> in January 2022, one of a series of online meetings held to fill the gap. The meeting addressed the basic biology of two key proteins implicated in chorea-acanthocytosis (mutations in <i>VPS13A</i>) and McLeod syndrome (mutations in <i>XK</i>). In a remarkable confluence of ideas, the speakers described different aspects of a single functional unit that comprises of VPS13A and XK proteins working together. Conditions caused by VPS13 (A-D) gene family mutations and related genes, such as XK, previously footnote knowledge, seem to turn central for a novel disease paradigm: bulk lipid transfer disorders.</p>","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"6 ","pages":"25152564231156994"},"PeriodicalIF":0.0,"publicationDate":"2023-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f9/5b/10.1177_25152564231156994.PMC10243564.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9718022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-22eCollection Date: 2023-01-01DOI: 10.1177/25152564231157706
Eliana Lara-Barba, Alba Torán-Vilarrubias, María Moriel-Carretero
The links between autophagy and genome stability, and whether they are important for lifespan and health, are not fully understood. We undertook a study to explore this notion at the molecular level using Saccharomyces cerevisiae. On the one hand, we triggered autophagy using rapamycin, to which we exposed mutants defective in preserving genome integrity, then assessed their viability, their ability to induce autophagy and the link between these two parameters. On the other hand, we searched for molecules derived from plant extracts known to have powerful benefits on human health to try to rescue the negative effects rapamycin had against some of these mutants. We uncover that autophagy execution is lethal for mutants unable to repair DNA double strand breaks, while the extract from Silybum marianum seeds induces an expansion of the endoplasmic reticulum (ER) that blocks autophagy and protects them. Our data uncover a connection between genome integrity and homeostasis of the ER whereby ER stress-like scenarios render cells tolerant to sub-optimal genome integrity conditions.
{"title":"An Expansion of the Endoplasmic Reticulum that Halts Autophagy is Permissive to Genome Instability.","authors":"Eliana Lara-Barba, Alba Torán-Vilarrubias, María Moriel-Carretero","doi":"10.1177/25152564231157706","DOIUrl":"10.1177/25152564231157706","url":null,"abstract":"<p><p>The links between autophagy and genome stability, and whether they are important for lifespan and health, are not fully understood. We undertook a study to explore this notion at the molecular level using <i>Saccharomyces cerevisiae</i>. On the one hand, we triggered autophagy using rapamycin, to which we exposed mutants defective in preserving genome integrity, then assessed their viability, their ability to induce autophagy and the link between these two parameters. On the other hand, we searched for molecules derived from plant extracts known to have powerful benefits on human health to try to rescue the negative effects rapamycin had against some of these mutants. We uncover that autophagy execution is lethal for mutants unable to repair DNA double strand breaks, while the extract from <i>Silybum marianum</i> seeds induces an expansion of the endoplasmic reticulum (ER) that blocks autophagy and protects them. Our data uncover a connection between genome integrity and homeostasis of the ER whereby ER stress-like scenarios render cells tolerant to sub-optimal genome integrity conditions.</p>","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"6 ","pages":"25152564231157706"},"PeriodicalIF":0.0,"publicationDate":"2023-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/06/bc/10.1177_25152564231157706.PMC10243512.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10291750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1177/25152564231185011
Ranran Mao, Chunfang Tong, Jia-Jia Liu
Endoplasmic reticulum (ER)-plasma membrane (PM) contact sites/junctions play important roles in cell physiology including signal transduction, ion and lipid transfer, and membrane dynamics. However, little is known about the dynamic regulation and functional roles of ER-PM junctions in neurons. Using a split green fluorescent protein-based membrane contact probe, we find that the density of ER-PM contact sites changes dynamically in the dendrites of hippocampal neurons undergoing long-term synaptic potentiation (LTP). We show that the Ca2±-sensing membrane tethering protein Extended Synaptotagmin 1 (E-Syt1) mediates the formation of ER-PM contact sites during LTP. We also show that E-Syt1 is required for neuronal activity-dependent surface expression of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-type glutamate receptors. These findings implicate ER-PM junctions in the regulation of neurotransmitter receptor trafficking and synaptic plasticity.
{"title":"E-Syt1 Regulates Neuronal Activity-Dependent Endoplasmic Reticulum-Plasma Membrane Junctions and Surface Expression of AMPA Receptors.","authors":"Ranran Mao, Chunfang Tong, Jia-Jia Liu","doi":"10.1177/25152564231185011","DOIUrl":"https://doi.org/10.1177/25152564231185011","url":null,"abstract":"<p><p>Endoplasmic reticulum (ER)-plasma membrane (PM) contact sites/junctions play important roles in cell physiology including signal transduction, ion and lipid transfer, and membrane dynamics. However, little is known about the dynamic regulation and functional roles of ER-PM junctions in neurons. Using a split green fluorescent protein-based membrane contact probe, we find that the density of ER-PM contact sites changes dynamically in the dendrites of hippocampal neurons undergoing long-term synaptic potentiation (LTP). We show that the Ca<sup>2</sup><sup>±</sup>-sensing membrane tethering protein Extended Synaptotagmin 1 (E-Syt1) mediates the formation of ER-PM contact sites during LTP. We also show that E-Syt1 is required for neuronal activity-dependent surface expression of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-type glutamate receptors. These findings implicate ER-PM junctions in the regulation of neurotransmitter receptor trafficking and synaptic plasticity.</p>","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"6 ","pages":"25152564231185011"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/81/db/10.1177_25152564231185011.PMC10359807.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10665745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1177/25152564231153621
Shintaro Fujimoto, Shinya Tashiro, Yasushi Tamura
Numerous studies have revealed that organelle membrane contact sites (MCSs) play important roles in diverse cellular events, including the transport of lipids and ions between connected organelles. To understand MCS functions, it is essential to uncover proteins that accumulate at MCSs. Here, we develop a complementation assay system termed CsFiND (Complementation assay using Fusion of split-GFP and TurboID) for the simultaneous visualization of MCSs and identification of MCS-localized proteins. We express the CsFiND proteins on the endoplasmic reticulum and mitochondrial outer membrane in yeast to verify the reliability of CsFiND as a tool for identifying MCS-localized proteins.
{"title":"Complementation Assay Using Fusion of Split-GFP and TurboID (CsFiND) Enables Simultaneous Visualization and Proximity Labeling of Organelle Contact Sites in Yeast.","authors":"Shintaro Fujimoto, Shinya Tashiro, Yasushi Tamura","doi":"10.1177/25152564231153621","DOIUrl":"https://doi.org/10.1177/25152564231153621","url":null,"abstract":"<p><p>Numerous studies have revealed that organelle membrane contact sites (MCSs) play important roles in diverse cellular events, including the transport of lipids and ions between connected organelles. To understand MCS functions, it is essential to uncover proteins that accumulate at MCSs. Here, we develop a complementation assay system termed CsFiND (Complementation assay using Fusion of split-GFP and TurboID) for the simultaneous visualization of MCSs and identification of MCS-localized proteins. We express the CsFiND proteins on the endoplasmic reticulum and mitochondrial outer membrane in yeast to verify the reliability of CsFiND as a tool for identifying MCS-localized proteins.</p>","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"6 ","pages":"25152564231153621"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/af/cc/10.1177_25152564231153621.PMC10243572.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10298544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1177/25152564221150428
Rohan P Singh, Yu-Ping Poh, Savar D Sinha, Jeremy G Wideman
Cells maintain the specific lipid composition of distinct organelles by vesicular transport as well as non-vesicular lipid trafficking via lipid transport proteins. Oxysterol-binding proteins (OSBPs) are a family of lipid transport proteins that transfer lipids at various membrane contact sites (MCSs). OSBPs have been extensively investigated in human and yeast cells where 12 have been identified in Homo sapiens and 7 in Saccharomyces cerevisiae. The evolutionary relationship between these well-characterized OSBPs is still unclear. By reconstructing phylogenies of eukaryote OSBPs, we show that the ancestral Saccharomycotina had four OSBPs, the ancestral fungus had five OSBPs, and the ancestral animal had six OSBPs, whereas the shared ancestor of animals and fungi as well as the ancestral eukaryote had only three OSBPs. Our analyses identified three undescribed ancient OSBP orthologues, one fungal OSBP (Osh8) lost in the lineage leading to yeast, one animal OSBP (ORP12) lost in the lineage leading to vertebrates, and one eukaryotic OSBP (OshEu) lost in both the animal and fungal lineages.
{"title":"Evolutionary History of Oxysterol-Binding Proteins Reveals Complex History of Duplication and Loss in Animals and Fungi.","authors":"Rohan P Singh, Yu-Ping Poh, Savar D Sinha, Jeremy G Wideman","doi":"10.1177/25152564221150428","DOIUrl":"https://doi.org/10.1177/25152564221150428","url":null,"abstract":"<p><p>Cells maintain the specific lipid composition of distinct organelles by vesicular transport as well as non-vesicular lipid trafficking via lipid transport proteins. Oxysterol-binding proteins (OSBPs) are a family of lipid transport proteins that transfer lipids at various membrane contact sites (MCSs). OSBPs have been extensively investigated in human and yeast cells where 12 have been identified in <i>Homo sapiens</i> and 7 in <i>Saccharomyces cerevisiae</i>. The evolutionary relationship between these well-characterized OSBPs is still unclear. By reconstructing phylogenies of eukaryote OSBPs, we show that the ancestral Saccharomycotina had four OSBPs, the ancestral fungus had five OSBPs, and the ancestral animal had six OSBPs, whereas the shared ancestor of animals and fungi as well as the ancestral eukaryote had only three OSBPs. Our analyses identified three undescribed ancient OSBP orthologues, one fungal OSBP (Osh8) lost in the lineage leading to yeast, one animal OSBP (ORP12) lost in the lineage leading to vertebrates, and one eukaryotic OSBP (OshEu) lost in both the animal and fungal lineages.</p>","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"6 ","pages":"25152564221150428"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10243569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10302701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}