Journal of cell science最新文献_第2页

Inpp5e Is Critical for Photoreceptor Outer Segment Maintenance.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-01-28 DOI: 10.1242/jcs.263814

Mohona Gupta, Tylor R Lewis, Michael W Stuck, William J Spencer, Natalia V Klementieva, Vadim Y Arshavsky, Gregory J Pazour

{"title":"Inpp5e Is Critical for Photoreceptor Outer Segment Maintenance.","authors":"Mohona Gupta, Tylor R Lewis, Michael W Stuck, William J Spencer, Natalia V Klementieva, Vadim Y Arshavsky, Gregory J Pazour","doi":"10.1242/jcs.263814","DOIUrl":"10.1242/jcs.263814","url":null,"abstract":"In humans, inositol polyphosphate-5-phosphatase e (INPP5E) mutations cause retinal degeneration as part of Joubert and MORM syndromes and can also cause non-syndromic blindness. In mice, mutations cause a spectrum of brain, kidney, and other anomalies and prevent the formation of photoreceptor outer segments. To further explore the function of Inpp5e in photoreceptors, we generated conditional and inducible knockouts of mouse Inpp5e where the gene was deleted either during outer segment formation or after outer segments were fully formed. In both cases, the loss of Inpp5e led to severe defects in photoreceptor outer segment morphology and ultimately photoreceptor cell loss. The primary morphological defect consisted of outer segment shortening and reduction in the number of newly forming discs at the outer segment base. This was accompanied by structural abnormalities of the Golgi apparatus, mislocalized rhodopsin, and an accumulation of extracellular vesicles. In addition, knockout cells showed disruption of the actin network. Together, these data demonstrate that Inpp5e plays a critical role in maintaining the outer segment and the normal process of outer segment renewal depends on the activity of this enzyme.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SuperResNET: Single molecule network analysis detects changes to clathrin structure by small molecule inhibitors. SuperResNET：单分子网络分析检测小分子抑制剂对凝集素结构的改变。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-01-27 DOI: 10.1242/jcs.263570

Timothy H Wong, Ismail M Khater, Christian Hallgrimson, Y Lydia Li, Ghassan Hamarneh, Ivan R Nabi

{"title":"SuperResNET: Single molecule network analysis detects changes to clathrin structure by small molecule inhibitors.","authors":"Timothy H Wong, Ismail M Khater, Christian Hallgrimson, Y Lydia Li, Ghassan Hamarneh, Ivan R Nabi","doi":"10.1242/jcs.263570","DOIUrl":"https://doi.org/10.1242/jcs.263570","url":null,"abstract":"Here, we apply SuperResNET network analysis of dSTORM single-molecule localization microscopy (SMLM) to determine how the clathrin endocytosis inhibitors pitstop 2, dynasore and Latrunculin A alter the morphology of clathrin-coated pits. SuperResNET analysis of HeLa and Cos7 cells identifies: small oligomers (Class I); pits and vesicles (Class II); and larger clusters corresponding to fused pits or clathrin plaques (Class III). Pitstop 2 and dynasore induce distinct homogeneous populations of Class II structures in HeLa cells suggesting that they arrest endocytosis at different stages. Inhibition is not via actin depolymerization, as the actin-depolymerizing agent latrunculin A (LatA) induces large, heterogeneous clathrin structures. Ternary analysis of SuperResNET shape features presents a distinct more planar profile for pitstop 2 blobs that align with clathrin pits identified with high-resolution MINFLUX, while control structures resemble MINFLUX clathrin vesicles. SuperResNET analysis therefore shows that pitstop 2 arrests clathrin pit maturation at early stages of pit formation, representing an approach to detect the effect of small molecules on target structures in situ in the cell from SMLM data sets.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dynein-driven regulation of postsynaptic membrane architecture and synaptic function.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-01-27 DOI: 10.1242/jcs.263844

Amanda L Neisch, Thomas Pengo, Adam W Avery, Min-Gang Li, Thomas S Hays

{"title":"Dynein-driven regulation of postsynaptic membrane architecture and synaptic function.","authors":"Amanda L Neisch, Thomas Pengo, Adam W Avery, Min-Gang Li, Thomas S Hays","doi":"10.1242/jcs.263844","DOIUrl":"https://doi.org/10.1242/jcs.263844","url":null,"abstract":"Cytoplasmic dynein is essential in motoneurons for retrograde cargo transport that sustains neuronal connectivity. Little, however, is known about dynein's function on the postsynaptic side of the circuit. Here we report distinct postsynaptic roles for dynein at neuromuscular junctions (NMJs). Intriguingly, we show that dynein punctae accumulate postsynaptically at glutamatergic synaptic terminals. Moreover, Skittles, a phosphatidylinositol 4-phosphate 5-kinase that produces PI(4,5)P2 to organize the spectrin cytoskeleton, also localizes specifically to glutamatergic synaptic terminals. Depletion of postsynaptic dynein disrupts the accumulation of Skittles, PI(4,5)P2 phospholipid, and organization of the spectrin cytoskeleton at the postsynaptic membrane. Coincidental with dynein depletion, we observe an increase in the size of ionotropic glutamate receptor (iGluRs) fields, and an increase in the amplitude and frequency of mEJPs. PI(4,5)P2 levels do not affect iGluR clustering, nor does dynein affect the levels of iGluR subunits at the NMJ. Our observations suggest a separate, transport independent function for dynein in iGluR cluster organization. Based on the close apposition of dynein punctae to the iGluR fields, we speculate that dynein at the postsynaptic membrane contributes to the organization of the receptor fields, hence ensuring proper synaptic transmission.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

γ-secretase facilitates retromer-mediated retrograde transport.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-01-27 DOI: 10.1242/jcs.263538

Yuka Takeo, Mac Crite, Kashif Mehmood, Daniel DiMaio

{"title":"γ-secretase facilitates retromer-mediated retrograde transport.","authors":"Yuka Takeo, Mac Crite, Kashif Mehmood, Daniel DiMaio","doi":"10.1242/jcs.263538","DOIUrl":"10.1242/jcs.263538","url":null,"abstract":"Retromer mediates retrograde transport of protein cargos from endosomes to the trans-Golgi network (TGN). γ-secretase is a protease that cleaves the transmembrane domain of its target proteins. Although retromer can form a stable complex with γ-secretase, the functional consequences of this interaction are not known. Here, we report that retromer-mediated retrograde protein trafficking in cultured human epithelial cells is impaired by the γ-secretase inhibitor XXI or by knockout of the catalytic subunit of γ-secretase. These treatments inhibited endosome to TGN trafficking of retromer-dependent retrograde cellular cargos, divalent metal transporter 1 isoform II, cation-independent mannose-6-phosphate receptor, and shiga toxin, whereas trafficking of retromer-independent cargos cholera toxin and a mutant CIMPR unable to bind retromer was not affected. Moreover, we found that g-secretase associates with retromer cargos even in the absence of retromer. XXI treatment and PS1 knockout did not inhibit the ability of retromer or g-secretase to associate with cargo and did not affect the expression of retromer subunits or Rab7-GTP, which regulates retromer-cargo interaction. These results imply that the γ-secretase-retromer interaction facilitates retromer-mediated retrograde trafficking of cellular transmembrane proteins.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Talin, a Rap1 effector for integrin activation at the plasma membrane, also promotes Rap1 activity by disrupting sequestration of Rap1 by SHANK3.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-01-24 DOI: 10.1242/jcs.263595

Zhongji Liao, Sanford J Shattil

{"title":"Talin, a Rap1 effector for integrin activation at the plasma membrane, also promotes Rap1 activity by disrupting sequestration of Rap1 by SHANK3.","authors":"Zhongji Liao, Sanford J Shattil","doi":"10.1242/jcs.263595","DOIUrl":"https://doi.org/10.1242/jcs.263595","url":null,"abstract":"Talin regulates the adhesion and migration of cells in part by promoting the affinity of integrins for extracellular matrix proteins, a process that in cells such as endothelial cells and platelets requires the direct interaction of talin with both the small GTPase, Rap1-GTP, and the integrin β3 cytoplasmic tail. To study this process in more detail, we employed an optogenetic approach in living, immortalized endothelial cells to be able to regulate talin interaction with the plasma membrane. Previous studies identified talin as the Rap1-GTP effector for β3 integrin activation. Surprisingly, optogenetic recruitment of talin to the plasma membrane also led to the localized activation of Rap1 itself, apparently by talin competing for Rap1-GTP with SHANK3, a protein known to sequester Rap1-GTP and to block integrin activation. Rap1 activation by talin was localized to the cell periphery in suspension cells and within lamellipodia and pseudopodia in cells adherent to fibronectin. Thus, membrane-associated talin can play a dual role in regulating integrin function in endothelial cells: first by releasing Rap1-GTP from its sequestration by SHANK3 and second by serving as the relevant Rap1 effector for integrin activation.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dynamic mechanisms for membrane skeleton transitions. 膜骨架转变的动力机制。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-01-22 DOI: 10.1242/jcs.263473

Mayte Bonilla-Quintana, Andrea Ghisleni, Nils C Gauthier, Padmini Rangamani

{"title":"Dynamic mechanisms for membrane skeleton transitions.","authors":"Mayte Bonilla-Quintana, Andrea Ghisleni, Nils C Gauthier, Padmini Rangamani","doi":"10.1242/jcs.263473","DOIUrl":"10.1242/jcs.263473","url":null,"abstract":"The plasma membrane and the underlying skeleton form a protective barrier for eukaryotic cells. The molecular players forming this complex composite material constantly rearrange under mechanical stress. One of those molecules, spectrin, is ubiquitous in the membrane skeleton and linked by short actin filaments. In this work, we developed a generalized network model for the membrane skeleton integrated with myosin contractility and membrane mechanics to investigate the response of the spectrin meshwork to mechanical loading. We observed that the force generated by membrane bending is important to maintain a regular skeletal structure suggesting that the membrane is not just supported by the skeleton, but has an active contribution to the stability of the cell structure. We found that spectrin and myosin turnover are necessary for the transition between stress and rest states in the skeleton. Simulations of a fully connected network representing a whole cell show that the surface area constraint of the plasma membrane and volume restriction of the cytoplasm enhance the stability of the membrane skeleton. Furthermore, we showed that cell attachment through adhesions promotes cell shape stabilization.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cadherins and Growth Factor Receptors: ligand selective mechano-switches at cadherin junctions. 钙粘蛋白和生长因子受体：钙粘蛋白连接处的配体选择性机械开关。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-01-16 DOI: 10.1242/jcs.262279

Vinh Vu, Brendan Sullivan, Evan Hebner, Zainab Rahil, Yubo Zou, Deborah Leckband

{"title":"Cadherins and Growth Factor Receptors: ligand selective mechano-switches at cadherin junctions.","authors":"Vinh Vu, Brendan Sullivan, Evan Hebner, Zainab Rahil, Yubo Zou, Deborah Leckband","doi":"10.1242/jcs.262279","DOIUrl":"https://doi.org/10.1242/jcs.262279","url":null,"abstract":"This study investigated possible mechanisms underlying differences between heterophilic and homophilic cadherin adhesions that influence intercellular mechanics and multicellular organization. Results suggest that homophilic cadherin ligation selectively activates force-transduction, such that resulting signaling and mechano-transduction amplitudes are independent of cadherin binding affinities. Epithelial (E-) and neural (N-) cadherin cooperate with distinct growth factors to mechanically activate force-transduction cascades. Prior results demonstrated that E-cadherin and epidermal growth factor receptor form force-sensitive complexes at intercellular junctions. Here, results show that the reconstitution of N-cadherin force transduction required the co-expression of N-cadherin and fibroblast growth factor receptor. Mechanical measurements further demonstrated that homophilic ligation initiates receptor tyrosine kinase-dependent force transduction cascades, but heterophilic cadherin ligands fail to activate signaling or generate stereotypical mechano-transduction signatures. The all-or-nothing contrast between mechano-transduction by heterophilic versus homophilic cadherin adhesions supersedes differences in cadherin adhesion strength. This mechano-selectivity impacts cell spreading and traction generation on cadherin substrates. Homophilic ligation appears to be a key that selectively unlocks cadherin mechano-transduction. These findings may reconcile the roles of cadherin recognition and cell mechanics in the organization of multicellular assemblies.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Classification and characteristics of bacterial glycosaminoglycan lyases, and their therapeutic and experimental applications.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-01-15 Epub Date: 2025-01-23 DOI: 10.1242/jcs.263489

Ruyi Zou, Xiangyu Xu, Fuchuan Li

{"title":"Classification and characteristics of bacterial glycosaminoglycan lyases, and their therapeutic and experimental applications.","authors":"Ruyi Zou, Xiangyu Xu, Fuchuan Li","doi":"10.1242/jcs.263489","DOIUrl":"https://doi.org/10.1242/jcs.263489","url":null,"abstract":"Glycosaminoglycans (GAGs), as animal polysaccharides, are linked to proteins to form various types of proteoglycans. Bacterial GAG lyases are not only essential enzymes that spoilage bacteria use for the degradation of GAGs, but also valuable tools for investigating the biological function and potential therapeutic applications of GAGs. The ongoing discovery and characterization of novel GAG lyases has identified an increasing number of lyases suitable for functional studies and other applications involving GAGs, which include oligosaccharide sequencing, detection and removal of specific glycan chains, clinical drug development and the design of novel biomaterials and sensors, some of which have not yet been comprehensively summarized. GAG lyases can be classified into hyaluronate lyases, chondroitinases and heparinases based on their substrate spectra, and their functional applications are mainly determined by their substrates, with different lyases exhibiting differing substrate selectivity and preferences. It is thus necessary to understand the properties of the available enzymes to determine strategies for their functional application. Building on previous studies and reviews, this Review highlights small yet crucial differences among or within the various GAG lyases to aid in optimizing their use in future studies. To clarify ideas and strategies for further research, we also discuss several traditional and novel applications of GAG lyases.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Meeting report - Alpine desmosome disease meeting 2024: advances and emerging topics in desmosomes and related diseases. 会议报告-高山桥粒病会议2024：桥粒和相关疾病的进展和新主题。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-01-15 Epub Date: 2025-01-22 DOI: 10.1242/jcs.263796

Jens Waschke, Masayuki Amagai, Christoph Becker, Mario Delmar, Firat Duru, David R Garrod, Brenda Gerull, Kathleen J Green, Michael Hertl, Andrew P Kowalczyk, Carien M Niessen, Asma Nusrat, Camilla Schinner, Nicolas Schlegel, Sanjeevi Sivasankar, Franziska Vielmuth, Volker Spindler

{"title":"Meeting report - Alpine desmosome disease meeting 2024: advances and emerging topics in desmosomes and related diseases.","authors":"Jens Waschke, Masayuki Amagai, Christoph Becker, Mario Delmar, Firat Duru, David R Garrod, Brenda Gerull, Kathleen J Green, Michael Hertl, Andrew P Kowalczyk, Carien M Niessen, Asma Nusrat, Camilla Schinner, Nicolas Schlegel, Sanjeevi Sivasankar, Franziska Vielmuth, Volker Spindler","doi":"10.1242/jcs.263796","DOIUrl":"https://doi.org/10.1242/jcs.263796","url":null,"abstract":"Desmosomes are adhesive cell contacts abundant in tissues exposed to mechanical strain, such as the stratified and simple epithelia of the epidermis and mucous membranes, as well as the myocardium. Besides their role in mechanical cell cohesion, desmosomes also modulate pathways important for tissue differentiation, wound healing and immune responses. Dysfunctional desmosomes, resulting from pathogenic variants in genes encoding desmosomal components, autoantibodies targeting desmosomal adhesion molecules or inflammation, cause the life-threatening diseases arrhythmogenic cardiomyopathy and pemphigus and contribute to the pathogenesis of inflammatory bowel diseases. The Alpine Desmosome Disease Meeting 2024 (ADDM 2024), held in Grainau, Germany in October 2024, connected international researchers from basic sciences with clinical experts from dermatology, cardiology, gastroenterology and surgery. The participants discussed recent advances, identified hot topics in desmosome biology and disease and provided new concepts for pathogenesis and treatment approaches.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cell migration signaling through the EGFR-VAV2-Rac1 pathway is sustained in endosomes. 通过EGFR-VAV2-Rac1途径的细胞迁移信号在内体中持续存在。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-01-15 Epub Date: 2025-01-24 DOI: 10.1242/jcs.263541

Itziar Pinilla-Macua, Sachin Surve, Alexander Sorkin

引用次数: 0