The abnormal protein degradation implicated in the pathogenesis of Parkinson's disease was previously attributed to defective H+ leakage from lysosomes via TMEM175 (https://doi.org/10.1016/j.cell.2022.05.021). In this issue, Riederer et al. (https://doi.org/10.1083/jcb.202501145) demonstrate that TMEM175 is instead a K+ channel, minimally permeable to H+.
{"title":"Is the Parkinson's-associated protein TMEM175 a proton channel: Yay or nay?","authors":"Spencer A Freeman,Sergio Grinstein","doi":"10.1083/jcb.202511084","DOIUrl":"https://doi.org/10.1083/jcb.202511084","url":null,"abstract":"The abnormal protein degradation implicated in the pathogenesis of Parkinson's disease was previously attributed to defective H+ leakage from lysosomes via TMEM175 (https://doi.org/10.1016/j.cell.2022.05.021). In this issue, Riederer et al. (https://doi.org/10.1083/jcb.202501145) demonstrate that TMEM175 is instead a K+ channel, minimally permeable to H+.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"1 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yang Yang,Qianjin Kong,Chaolian Liu,Fengyang Wang,Meijiao Li,Shalan Li,Yuehui Shi,Leonard Krall,Xin Wang,Shan He,Kai Jiang,Xuna Wu,Mei Yang,Chonglin Yang
Lysosomes are degradation and signaling organelles central to metabolic homeostasis. It remains unclear whether and how harmful metabolites compromise lysosome function in the etiopathology of metabolic disorders. Combining Caenorhabditiselegans and mouse models, we demonstrate that homocysteine, an intermediate in methionine-cysteine metabolism and the cause of the life-threatening disease homocystinuria, disrupts lysosomal functions. In C. elegans, mutations in cystathionine β-synthase cause strong buildup of homocysteine and developmental arrest. We reveal that homocysteine binds to and homocysteinylates V-ATPase, causing its inhibition and consequently impairment of lysosomal degradative capacity. This leads to enormous enlargement of lysosomes with extensive cargo accumulation and lysosomal membrane damage in severe cases. Cbs-deficient mice similarly accumulate homocysteine, displaying abnormal or damaged lysosomes reminiscent of lysosomal storage diseases in multiple tissues. These findings not only uncover how a metabolite can damage lysosomes but also establish lysosomal impairment as a critical contributing factor to homocystinuria and homocysteine-related diseases.
{"title":"Homocysteine disrupts lysosomal function by V-ATPase inhibition.","authors":"Yang Yang,Qianjin Kong,Chaolian Liu,Fengyang Wang,Meijiao Li,Shalan Li,Yuehui Shi,Leonard Krall,Xin Wang,Shan He,Kai Jiang,Xuna Wu,Mei Yang,Chonglin Yang","doi":"10.1083/jcb.202503081","DOIUrl":"https://doi.org/10.1083/jcb.202503081","url":null,"abstract":"Lysosomes are degradation and signaling organelles central to metabolic homeostasis. It remains unclear whether and how harmful metabolites compromise lysosome function in the etiopathology of metabolic disorders. Combining Caenorhabditiselegans and mouse models, we demonstrate that homocysteine, an intermediate in methionine-cysteine metabolism and the cause of the life-threatening disease homocystinuria, disrupts lysosomal functions. In C. elegans, mutations in cystathionine β-synthase cause strong buildup of homocysteine and developmental arrest. We reveal that homocysteine binds to and homocysteinylates V-ATPase, causing its inhibition and consequently impairment of lysosomal degradative capacity. This leads to enormous enlargement of lysosomes with extensive cargo accumulation and lysosomal membrane damage in severe cases. Cbs-deficient mice similarly accumulate homocysteine, displaying abnormal or damaged lysosomes reminiscent of lysosomal storage diseases in multiple tissues. These findings not only uncover how a metabolite can damage lysosomes but also establish lysosomal impairment as a critical contributing factor to homocystinuria and homocysteine-related diseases.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"10 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shuai Liu,Lina Ma,Ruiqi Lv,Liangting Guo,Xing Pan,Shufan Hu,Shan Li
Mitophagy transports mitochondria to lysosomes for degradation to maintain energy homeostasis, inflammation, and immunity. Here, we identify CipB, a type III secretion system (T3SS) effector from Chromobacterium violaceum, as a novel exogenous mitophagy receptor. CipB targets mitochondria by the mitochondrial protein TUFM and recruits autophagosomes via its LC3-interacting region (LIR) motifs. This process initiates the mitophagy-TFEB axis, triggering TFEB nuclear translocation and suppression of proinflammatory cytokines, thereby promoting bacterial survival and pathogenesis. CipB represents a conserved family of T3SS effectors employed by diverse pathogens to manipulate host mitophagy. Using a mouse model, CipB's mitophagy receptor function is critical for C. violaceum colonization in the liver and spleen, underscoring its role in bacterial virulence. This study reveals a novel mechanism by which bacterial pathogens exploit host mitophagy to suppress immune responses, defining CipB as a paradigm for exogenous mitophagy receptors. These findings advance our understanding of pathogen-host interactions and highlight the mitophagy-TFEB axis as a potential signaling pathway against bacterial infection.
{"title":"Bacterial CipB is an exogenous receptor to drive the mitophagy-TFEB axis and promote pathogenesis.","authors":"Shuai Liu,Lina Ma,Ruiqi Lv,Liangting Guo,Xing Pan,Shufan Hu,Shan Li","doi":"10.1083/jcb.202503028","DOIUrl":"https://doi.org/10.1083/jcb.202503028","url":null,"abstract":"Mitophagy transports mitochondria to lysosomes for degradation to maintain energy homeostasis, inflammation, and immunity. Here, we identify CipB, a type III secretion system (T3SS) effector from Chromobacterium violaceum, as a novel exogenous mitophagy receptor. CipB targets mitochondria by the mitochondrial protein TUFM and recruits autophagosomes via its LC3-interacting region (LIR) motifs. This process initiates the mitophagy-TFEB axis, triggering TFEB nuclear translocation and suppression of proinflammatory cytokines, thereby promoting bacterial survival and pathogenesis. CipB represents a conserved family of T3SS effectors employed by diverse pathogens to manipulate host mitophagy. Using a mouse model, CipB's mitophagy receptor function is critical for C. violaceum colonization in the liver and spleen, underscoring its role in bacterial virulence. This study reveals a novel mechanism by which bacterial pathogens exploit host mitophagy to suppress immune responses, defining CipB as a paradigm for exogenous mitophagy receptors. These findings advance our understanding of pathogen-host interactions and highlight the mitophagy-TFEB axis as a potential signaling pathway against bacterial infection.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"11 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145559235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Integrin-mediated cell-matrix adhesions regulate communication between cells and the extracellular matrix. In matrix-secreting cells, fibrillar adhesions (FBs) containing high levels of α5β1 integrins and the tensin3 adaptor protein are essential for fibronectin (FN) fibrillogenesis. Here, we demonstrate that tensin3 binds to four helical regions (R3, R4, R8, and R11) of talin, the principal integrin activator. Structural analysis revealed the residues critical for the tensin3-talin interaction, and mutational analysis showed that talin R8 and R11 are essential for FB formation and FN fibrillogenesis. Cellular experiments demonstrate that tensin3 binding to talin not only regulates integrin activation, but also modulates tensin3's propensity to undergo liquid-liquid phase separation (LLPS). Formation of such LLPS condensates increased when cells were plated on soft substrates compared with stiff ones. This effect was abolished by blocking the interaction between tensin3 and talin. Our data suggest a model in which LLPS condensates provide a signaling platform involved in cellular responses to sudden changes in tissue mechanics.
{"title":"Talin-tensin3 interactions regulate fibrillar adhesion formation and tensin3 phase separation.","authors":"Xingchen Li,Rafaella Konstantinou,Vinod Kumar Meena,Saba Notash,Komal Khalil,Tom Whalley,Paul Atherton,Igor Barsukov,Thomas Zacharchenko,Christoph Ballestrem","doi":"10.1083/jcb.202503155","DOIUrl":"https://doi.org/10.1083/jcb.202503155","url":null,"abstract":"Integrin-mediated cell-matrix adhesions regulate communication between cells and the extracellular matrix. In matrix-secreting cells, fibrillar adhesions (FBs) containing high levels of α5β1 integrins and the tensin3 adaptor protein are essential for fibronectin (FN) fibrillogenesis. Here, we demonstrate that tensin3 binds to four helical regions (R3, R4, R8, and R11) of talin, the principal integrin activator. Structural analysis revealed the residues critical for the tensin3-talin interaction, and mutational analysis showed that talin R8 and R11 are essential for FB formation and FN fibrillogenesis. Cellular experiments demonstrate that tensin3 binding to talin not only regulates integrin activation, but also modulates tensin3's propensity to undergo liquid-liquid phase separation (LLPS). Formation of such LLPS condensates increased when cells were plated on soft substrates compared with stiff ones. This effect was abolished by blocking the interaction between tensin3 and talin. Our data suggest a model in which LLPS condensates provide a signaling platform involved in cellular responses to sudden changes in tissue mechanics.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"51 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145559233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Microtubule-severing enzymes are evolutionarily conserved AAA-ATPases that sever microtubules, thereby regulating diverse microtubule-dependent cellular processes. How these enzymes couple Microtubule binding with ATP hydrolysis to trigger microtubule-remodeling remains poorly understood. Using Caenorhabditiselegans Katanin, which contains the MEI-1 catalytic AAA+ p60 and MEI-2 p80-like regulatory subunits, we identify a critical regulatory role of the N-terminal domain of MEI-1 in Katanin regulation. We demonstrate this domain represses the AAA+ core in cis, limiting ATP hydrolysis and preventing interaction with tubulin C-terminal tails in the absence of MEI-2. Strikingly, MEI-1 lacking its N terminus is constitutively active, enabling identification of pore residues critical for sensing microtubule C-terminal tails and relaying this signal to the AAA+ core. These findings reveal how Katanin activation is coupled to microtubule binding, thereby avoiding futile ATP hydrolysis. Given Katanin's evolutionary conservation, our work provides a mechanistic framework for its regulation in other organisms, with broader implications for human pathologies, including neurodegeneration and cancer.
{"title":"Intramolecular regulation of the MT-severing enzyme Katanin prevents futile ATP hydrolysis.","authors":"Nicolas Joly,Lionel Pintard","doi":"10.1083/jcb.202506192","DOIUrl":"https://doi.org/10.1083/jcb.202506192","url":null,"abstract":"Microtubule-severing enzymes are evolutionarily conserved AAA-ATPases that sever microtubules, thereby regulating diverse microtubule-dependent cellular processes. How these enzymes couple Microtubule binding with ATP hydrolysis to trigger microtubule-remodeling remains poorly understood. Using Caenorhabditiselegans Katanin, which contains the MEI-1 catalytic AAA+ p60 and MEI-2 p80-like regulatory subunits, we identify a critical regulatory role of the N-terminal domain of MEI-1 in Katanin regulation. We demonstrate this domain represses the AAA+ core in cis, limiting ATP hydrolysis and preventing interaction with tubulin C-terminal tails in the absence of MEI-2. Strikingly, MEI-1 lacking its N terminus is constitutively active, enabling identification of pore residues critical for sensing microtubule C-terminal tails and relaying this signal to the AAA+ core. These findings reveal how Katanin activation is coupled to microtubule binding, thereby avoiding futile ATP hydrolysis. Given Katanin's evolutionary conservation, our work provides a mechanistic framework for its regulation in other organisms, with broader implications for human pathologies, including neurodegeneration and cancer.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"8 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145545357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tianqi Wang,Daniel H Kim,Chang Ding,Dingxun Wang,Weiwei Zhang,Martin Silic,Xi Cheng,Kunming Shao,TingHsuan Ku,Conwy Zheng,Junkai Xie,Shulan Xiao,Krishna Jayant,Chongli Yuan,Alexander A Chubykin,Christopher J Staiger,GuangJun Zhang,Qing Deng
Potassium channels control membrane potential and various physiological processes, including cell migration. However, the specific role of inwardly rectifying potassium channels in immune cell chemotaxis remains unknown. Here, we demonstrate that inwardly rectifying potassium channels, particularly Kir7.1 (Kcnj13), maintain the resting membrane potential and are crucial for directional sensing during neutrophil chemotaxis. Blocking or knocking out Kir in neutrophils disrupted their ability to sense direction toward different chemoattractants in multiple models. Using genetically encoded voltage indicators, we observed oscillating hyperpolarization during tail retraction in zebrafish neutrophils, with Kir7.1 required for depolarization toward the chemokine source. Focal depolarization via optogenetics biased pseudopod selection and triggered new protrusions, which depended on Gα signaling. Global hyperpolarization caused neutrophils to stall migration. Additionally, Kir influences GPCR signaling activation in dHL-60 cells. This research introduces membrane potential as a key component of the complex feedforward mechanism that links the adaptive and excitable networks necessary to guide immune cells in challenging tissue environments.
{"title":"Inwardly rectifying potassium channels promote directional sensing during neutrophil chemotaxis.","authors":"Tianqi Wang,Daniel H Kim,Chang Ding,Dingxun Wang,Weiwei Zhang,Martin Silic,Xi Cheng,Kunming Shao,TingHsuan Ku,Conwy Zheng,Junkai Xie,Shulan Xiao,Krishna Jayant,Chongli Yuan,Alexander A Chubykin,Christopher J Staiger,GuangJun Zhang,Qing Deng","doi":"10.1083/jcb.202503037","DOIUrl":"https://doi.org/10.1083/jcb.202503037","url":null,"abstract":"Potassium channels control membrane potential and various physiological processes, including cell migration. However, the specific role of inwardly rectifying potassium channels in immune cell chemotaxis remains unknown. Here, we demonstrate that inwardly rectifying potassium channels, particularly Kir7.1 (Kcnj13), maintain the resting membrane potential and are crucial for directional sensing during neutrophil chemotaxis. Blocking or knocking out Kir in neutrophils disrupted their ability to sense direction toward different chemoattractants in multiple models. Using genetically encoded voltage indicators, we observed oscillating hyperpolarization during tail retraction in zebrafish neutrophils, with Kir7.1 required for depolarization toward the chemokine source. Focal depolarization via optogenetics biased pseudopod selection and triggered new protrusions, which depended on Gα signaling. Global hyperpolarization caused neutrophils to stall migration. Additionally, Kir influences GPCR signaling activation in dHL-60 cells. This research introduces membrane potential as a key component of the complex feedforward mechanism that links the adaptive and excitable networks necessary to guide immune cells in challenging tissue environments.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"167 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145545327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Camilla S Teng,Sarah W Curtis,Grace C Brewer,Elizabeth J Leslie-Clarkson,Jeffrey O Bush
Tissue fusion is integral to mammalian morphogenesis, and its failure is a significant cause of structural anomalies, yet the underlying cellular mechanisms are incompletely understood. We examine cellular drivers of upper lip fusion in the mammalian embryo by establishing a live-imaging modality, revealing specific enrichment of F-actin that propagates in multicellular cables anchored at the fusion site. Actomyosin contractility drives lip fusion, and its pharmacological or genetic attenuation results in failed fusion and cleft lip. Generating a series of mice deficient in specific p120-catenin molecular functions, we reveal that p120-catenin binding to RhoA and Kaiso is dispensable during mammalian development, while stabilization of cadherins is crucial. Through generating an allelic series of new compound P-cadherin/E-cadherin mouse mutations disrupting combined cadherin levels, we unveil an elevated cadherin cell adhesion threshold requirement specific to upper lip fusion. Finally, we identify CDH3 variants in individuals with cleft lip, supporting the relevance of this mechanism in human tissue fusion.
{"title":"Actomyosin contractility and a threshold of cadherin cell adhesion are required during tissue fusion.","authors":"Camilla S Teng,Sarah W Curtis,Grace C Brewer,Elizabeth J Leslie-Clarkson,Jeffrey O Bush","doi":"10.1083/jcb.202503070","DOIUrl":"https://doi.org/10.1083/jcb.202503070","url":null,"abstract":"Tissue fusion is integral to mammalian morphogenesis, and its failure is a significant cause of structural anomalies, yet the underlying cellular mechanisms are incompletely understood. We examine cellular drivers of upper lip fusion in the mammalian embryo by establishing a live-imaging modality, revealing specific enrichment of F-actin that propagates in multicellular cables anchored at the fusion site. Actomyosin contractility drives lip fusion, and its pharmacological or genetic attenuation results in failed fusion and cleft lip. Generating a series of mice deficient in specific p120-catenin molecular functions, we reveal that p120-catenin binding to RhoA and Kaiso is dispensable during mammalian development, while stabilization of cadherins is crucial. Through generating an allelic series of new compound P-cadherin/E-cadherin mouse mutations disrupting combined cadherin levels, we unveil an elevated cadherin cell adhesion threshold requirement specific to upper lip fusion. Finally, we identify CDH3 variants in individuals with cleft lip, supporting the relevance of this mechanism in human tissue fusion.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"29 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145499604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell rounding during mitosis necessitates adaptive remodeling of plasma membrane and cortical cytoskeleton. However, the underlying mechanisms remain poorly elucidated. Here, we have identified Numb phosphorylation as a pivotal mechanism in the membrane-cytoskeleton remodeling associated with mitotic cell rounding. Upon mitotic entry, Aurora A phosphorylates Numb, leading to the dissociation of Numb from plasma membrane. This is crucial for proper plasma membrane retraction, since overexpression of a non-phosphorylatable mutant or a constitutively membrane-bound variant of Numb dramatically disrupts mitotic plasma membrane retraction. Mechanistically, releasing Numb from the plasma membrane enhances the myosin I-mediated membrane-to-cortex adhesion, thereby facilitating the plasma membrane retraction accompanied with cytoskeletal withdrawal. Further analysis showed that compromised plasma membrane retraction confines mitotic cell rounding and consequently leads to spindle orientation defects. Thus, our study elucidates a phosphorylation-mediated mechanism underlying plasma membrane retraction and underscores the functional importance of this process in the context of mitotic cell rounding.
{"title":"Adapting plasma membrane for mitotic cell rounding through Aurora A phosphorylation of numb.","authors":"Yanyan Li,Ke Liu,Xian Lin,Zhihao Ding,Haiyan Sun,Xiangyun Liao,Binghua Cheng,Wenli Shi,Junde Xu,Jiaming Liang,Zeyu Zhou,Wenjie Zhou,Hui Tian,Long Meng,Guangyong Chen,Ximing Shao,Hongchang Li","doi":"10.1083/jcb.202412005","DOIUrl":"https://doi.org/10.1083/jcb.202412005","url":null,"abstract":"Cell rounding during mitosis necessitates adaptive remodeling of plasma membrane and cortical cytoskeleton. However, the underlying mechanisms remain poorly elucidated. Here, we have identified Numb phosphorylation as a pivotal mechanism in the membrane-cytoskeleton remodeling associated with mitotic cell rounding. Upon mitotic entry, Aurora A phosphorylates Numb, leading to the dissociation of Numb from plasma membrane. This is crucial for proper plasma membrane retraction, since overexpression of a non-phosphorylatable mutant or a constitutively membrane-bound variant of Numb dramatically disrupts mitotic plasma membrane retraction. Mechanistically, releasing Numb from the plasma membrane enhances the myosin I-mediated membrane-to-cortex adhesion, thereby facilitating the plasma membrane retraction accompanied with cytoskeletal withdrawal. Further analysis showed that compromised plasma membrane retraction confines mitotic cell rounding and consequently leads to spindle orientation defects. Thus, our study elucidates a phosphorylation-mediated mechanism underlying plasma membrane retraction and underscores the functional importance of this process in the context of mitotic cell rounding.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"81 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Samantha E Ryken,Shu-Zon Wu,Matias L Lee,Miranda M Greig,Nika M Recto,Sophia Chang Stauffer,Carlisle S Bascom,Eric M Kramer,Magdalena Bezanilla
Polarized growth drives the morphogenesis of elongated cellular structures. In plants, polarized growth depends on actin and a tip focused ionic calcium gradient. How the calcium gradient is maintained remains unclear. We discovered that autoinhibitory calcium ATPases (ACAs) redundantly contribute to the steepness of the calcium gradient. ACA1 and ACA2 localize to the subapical plasma membrane and ACA5 to the vacuole membrane, providing spatial regulation of calcium efflux. Tip-growing plant cells also exhibit apical calcium fluctuations. Even though Δaca1/2/5 cells have a diminished calcium gradient, they exhibit normal fluctuations and actin but have significantly reduced apical secretion. Furthermore, cells lacking apical actin retain a strong calcium gradient but have reduced apical secretion. Suppression of both the calcium gradient and apical actin dramatically impairs growth, supporting a model where two independent and parallel processes, the calcium gradient and apical actin, promote rapid polarized growth.
{"title":"Autoinhibitory calcium ATPases regulate the calcium gradient required for rapid polarized growth.","authors":"Samantha E Ryken,Shu-Zon Wu,Matias L Lee,Miranda M Greig,Nika M Recto,Sophia Chang Stauffer,Carlisle S Bascom,Eric M Kramer,Magdalena Bezanilla","doi":"10.1083/jcb.202506021","DOIUrl":"https://doi.org/10.1083/jcb.202506021","url":null,"abstract":"Polarized growth drives the morphogenesis of elongated cellular structures. In plants, polarized growth depends on actin and a tip focused ionic calcium gradient. How the calcium gradient is maintained remains unclear. We discovered that autoinhibitory calcium ATPases (ACAs) redundantly contribute to the steepness of the calcium gradient. ACA1 and ACA2 localize to the subapical plasma membrane and ACA5 to the vacuole membrane, providing spatial regulation of calcium efflux. Tip-growing plant cells also exhibit apical calcium fluctuations. Even though Δaca1/2/5 cells have a diminished calcium gradient, they exhibit normal fluctuations and actin but have significantly reduced apical secretion. Furthermore, cells lacking apical actin retain a strong calcium gradient but have reduced apical secretion. Suppression of both the calcium gradient and apical actin dramatically impairs growth, supporting a model where two independent and parallel processes, the calcium gradient and apical actin, promote rapid polarized growth.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"30 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145433769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In eukaryotes, membrane-bound organelles create distinct molecular environments. The compartmentalizing lipid bilayer is a dynamic composite material whose thickness and curvature modulate the structure and function of membrane proteins. In vitro, bilayer thickness correlates with lipid composition. Cellular membranes in situ, however, are continuously remodeled, and the spatial variation of their biophysical properties remains understudied. Here, we present a computational approach to measure local membrane thickness in cryo-electron tomograms. Our analysis of Chlamydomonas reinhardtii and human cells reveals systematic thickness variations within and across organelles. Notably, we observe thickness gradients across the Golgi apparatus that orthogonally support long-standing models of differential sorting of transmembrane proteins based on hydrophobic matching. Our publicly available workflow readily integrates within existing tomogram analysis pipelines and, when applied across experimental systems, provides a quantitative foundation for exploring relationships between membrane thickness and function in native cellular environments.
{"title":"Systematic membrane thickness variation across cellular organelles revealed by cryo-ET.","authors":"Desislava Glushkova,Stefanie Böhm,Martin Beck","doi":"10.1083/jcb.202504053","DOIUrl":"https://doi.org/10.1083/jcb.202504053","url":null,"abstract":"In eukaryotes, membrane-bound organelles create distinct molecular environments. The compartmentalizing lipid bilayer is a dynamic composite material whose thickness and curvature modulate the structure and function of membrane proteins. In vitro, bilayer thickness correlates with lipid composition. Cellular membranes in situ, however, are continuously remodeled, and the spatial variation of their biophysical properties remains understudied. Here, we present a computational approach to measure local membrane thickness in cryo-electron tomograms. Our analysis of Chlamydomonas reinhardtii and human cells reveals systematic thickness variations within and across organelles. Notably, we observe thickness gradients across the Golgi apparatus that orthogonally support long-standing models of differential sorting of transmembrane proteins based on hydrophobic matching. Our publicly available workflow readily integrates within existing tomogram analysis pipelines and, when applied across experimental systems, provides a quantitative foundation for exploring relationships between membrane thickness and function in native cellular environments.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"1 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145433770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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