Journal of cell science最新文献_第6页

Inpp5e is crucial for photoreceptor outer segment maintenance.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-02-15 Epub Date: 2025-02-21 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 crucial 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, 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 crucial 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":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883294/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TC10 on endosomes regulates the local balance between microtubule stability and dynamics through the PAK2-JNK pathway and promotes axon outgrowth.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-02-15 Epub Date: 2025-02-26 DOI: 10.1242/jcs.263636

Shingo Koinuma, Misa Miyaji, Suzuka Akiyama, Yasuyuki Ito, Hiroshi Takemura, Naoyuki Wada, Michihiro Igarashi, Takeshi Nakamura

{"title":"TC10 on endosomes regulates the local balance between microtubule stability and dynamics through the PAK2-JNK pathway and promotes axon outgrowth.","authors":"Shingo Koinuma, Misa Miyaji, Suzuka Akiyama, Yasuyuki Ito, Hiroshi Takemura, Naoyuki Wada, Michihiro Igarashi, Takeshi Nakamura","doi":"10.1242/jcs.263636","DOIUrl":"https://doi.org/10.1242/jcs.263636","url":null,"abstract":"The neuronal cytoskeleton comprises microtubules, actin filaments and neurofilaments, and plays a crucial role in axon outgrowth and transport. Microtubules and actin filaments have attracted considerable attention in axon regeneration studies. We have previously shown that TC10 (also known as RhoQ), a Rho family GTPase that promotes axon outgrowth through membrane addition, is required for efficient axon regeneration. This study demonstrates that TC10 on recycling endosomes, but not on the plasma membrane, balances microtubule stability and dynamics in the axons, thereby counteracting axon retraction. TC10 ablation reduced the phosphorylation of SCG10 (also known as STMN2) and MAP1B, which are neuronal microtubule-binding proteins and JNK substrates. Consistent with this, JNK phosphorylation was decreased in TC10-knockout neurons compared to in wild-type neurons. Furthermore, TC10 deletion significantly reduced PAK2 autophosphorylation. PAK2 was found on Rab11-positive endosomes in cell bodies and axons, and its localization to endosomes was reduced by TC10 loss. PAK inhibition reduced tubulin acetylation and JNK phosphorylation in axons. Furthermore, MKK4 and MKK7 (also known as MAP2K4 and MAP2K7, respectively) were found to mediate signaling from TC10-activated PAK to JNK on JIP1-positive endosomes. Overall, TC10 transmits a microtubule-regulatory signal from PAK2 to SCG10 and MAP1B via JNK on axonal endosomes.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143501417","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 crosstalk between cytoskeletal filaments regulates dorsoventral cytoplasmic mechanics.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-02-15 Epub Date: 2025-02-27 DOI: 10.1242/jcs.263464

Dipanjan Ray, Deepak Kumar Sinha

{"title":"Dynamic crosstalk between cytoskeletal filaments regulates dorsoventral cytoplasmic mechanics.","authors":"Dipanjan Ray, Deepak Kumar Sinha","doi":"10.1242/jcs.263464","DOIUrl":"10.1242/jcs.263464","url":null,"abstract":"The cytoplasm exhibits viscoelastic properties, displaying both solid and liquid-like behaviour, and can actively regulate its mechanical attributes. The cytoskeleton is a major regulator among the numerous factors influencing cytoplasmic mechanics. We explore the interdependence of various cytoskeletal filaments and the impact of their density on cytoplasmic viscoelasticity. The heterogeneous distribution of these filaments gives rise to polarised mechanical properties of the cytoplasm along the dorsoventral axis. Actin filament disassembly softens the ventral cytoplasm while stiffening the mid cytoplasm, due to increased vimentin filament assembly. Disruption of microtubules or depletion of vimentin softens both the ventral and mid cytoplasm. Cytochalasin D (Cyto D) treatment results in a localised increase of vimentin assembly in the mid cytoplasm, which is dependent on the cytolinker plectin. Nocodazole treatment has a negligible effect on F-actin distribution but significantly alters the spatial arrangement of vimentin. We demonstrate that Cyto D treatment upregulates vimentin expression via reactive oxygen species-mediated activation of NF-κΒ. This article investigates how different cytoskeletal filaments influence the rheological characteristics of various cytoplasmic regions.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065973","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 : 2025-02-15 Epub Date: 2025-02-26 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":"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 bound to GTP (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 the interaction of talin with the plasma membrane. Previous studies identified talin as the Rap1-GTP effector for β3 integrin activation. Surprisingly, optogenetic recruitment of talin-1 (TLN1; herein referred to as 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":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928058/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The importance of delivering Recherche d'Avenir - research for the future.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-02-15 Epub Date: 2025-02-24 DOI: 10.1242/jcs.263909

Renata Basto

引用次数: 0

The emerging roles of the endoplasmic reticulum in mechanosensing and mechanotransduction.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-02-15 Epub Date: 2025-02-20 DOI: 10.1242/jcs.263503

Jonathan Townson, Cinzia Progida

{"title":"The emerging roles of the endoplasmic reticulum in mechanosensing and mechanotransduction.","authors":"Jonathan Townson, Cinzia Progida","doi":"10.1242/jcs.263503","DOIUrl":"https://doi.org/10.1242/jcs.263503","url":null,"abstract":"Cells are continuously subjected to physical and chemical cues from the extracellular environment, and sense and respond to mechanical cues via mechanosensation and mechanotransduction. Although the role of the cytoskeleton in these processes is well known, the contribution of intracellular membranes has been long neglected. Recently, it has become evident that various organelles play active roles in both mechanosensing and mechanotransduction. In this Review, we focus on mechanosensitive roles of the endoplasmic reticulum (ER), the functions of which are crucial for maintaining cell homeostasis. We discuss the effects of mechanical stimuli on interactions between the ER, the cytoskeleton and other organelles; the role of the ER in intracellular Ca2+ signalling via mechanosensitive channels; and how the unfolded protein response and lipid homeostasis contribute to mechanosensing. The expansive structure of the ER positions it as a key intracellular communication hub, and we additionally explore how this may be leveraged to transduce mechanical signals around the cell. By synthesising current knowledge, we aim to shed light on the emerging roles of the ER in cellular mechanosensing and mechanotransduction.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458139","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

TAZ interactome analysis using nanotrap-based affinity purification-mass spectrometry.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-02-15 Epub Date: 2025-02-24 DOI: 10.1242/jcs.263527

Jonathan Kelebeev, Anastasia MacKeracher, Tetsuaki Miyake, John C McDermott

{"title":"TAZ interactome analysis using nanotrap-based affinity purification-mass spectrometry.","authors":"Jonathan Kelebeev, Anastasia MacKeracher, Tetsuaki Miyake, John C McDermott","doi":"10.1242/jcs.263527","DOIUrl":"10.1242/jcs.263527","url":null,"abstract":"Characterization of protein-protein interactions (PPIs) is a fundamental goal in the post-genomic era. Here, we document a generally applicable approach to identify cellular protein interactomes using a combination of nanobody-based affinity purification (AP) coupled with liquid chromatography and tandem mass spectrometry (LC-MS/MS). The Hippo signaling regulator TAZ (also known as WWTR1) functions as a transcriptional co-repressor or activator depending on its PPI network; we therefore undertook an unbiased proteomic screen to identify TAZ PPIs in striated muscle cells. A GFP nanotrap-based AP approach coupled with protein identification through LC-MS/MS was used to document a comprehensive list of known and novel TAZ interactome components. Informatic analysis of the interactome documented known components of the Hippo signaling pathway and multiple epigenetic regulators such as the NuRD, FACT and SWI/SNF complexes and the pro-myogenic CARM1 methyltransferase. Hippo pathway reporter gene (HOP/HIP) analysis indicated that CARM1 represses TAZ transcriptional co-activator function, promoting TAZ Ser89 phosphorylation and TAZ cytoplasmic sequestration. MS analysis revealed that CARM1 dimethylates TAZ at Arg77 in a PGPR*LAGG consensus peptide, resulting in enhanced TAZ Ser89 phosphorylation. These studies underline the utility of a nanobody-based AP approach for interactome analysis.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","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 : 2025-02-15 Epub Date: 2025-02-28 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 integrating 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 in maintaining a regular skeletal structure, suggesting that the membrane is not just supported by the skeleton, but actively contributes towards 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":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928055/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Actin from within - how nuclear myosins and actin regulate nuclear architecture and mechanics.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-02-01 Epub Date: 2025-02-10 DOI: 10.1242/jcs.263550

Marta Gawor, Lilya Lehka, Danielle Lambert, Christopher P Toseland

{"title":"Actin from within - how nuclear myosins and actin regulate nuclear architecture and mechanics.","authors":"Marta Gawor, Lilya Lehka, Danielle Lambert, Christopher P Toseland","doi":"10.1242/jcs.263550","DOIUrl":"10.1242/jcs.263550","url":null,"abstract":"Over the past two decades, significant progress has been made in understanding mechanotransduction to the nucleus. Nevertheless, most research has focused on outside-in signalling orchestrated by external mechanical stimuli. Emerging evidence highlights the importance of intrinsic nuclear mechanisms in the mechanoresponse. The discovery of actin and associated motor proteins, such as myosins, in the nucleus, along with advances in chromatin organisation research, has raised new questions about the contribution of intranuclear architecture and mechanics. Nuclear actin and myosins are present in various compartments of the nucleus, particularly at sites of DNA processing and modification. These proteins can function as hubs and scaffolds, cross-linking distant chromatin regions and thereby impacting local and global nuclear membrane shape. Importantly, nuclear myosins are force-sensitive and nuclear actin cooperates with mechanosensors, suggesting a multi-level contribution to nuclear mechanics. The crosstalk between nuclear myosins and actin has significant implications for cell mechanical plasticity and the prevention of pathological conditions. Here, we review the recent impactful findings that highlight the roles of nuclear actin and myosins in nuclear organisation. Additionally, we discuss potential links between these proteins and emphasize the importance of using new methodologies to unravel nuclear-derived regulatory mechanisms distinct from the cytoskeleton.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clearing the path for whole-mount labeling and quantification of neuron and vessel density in adipose tissue.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-02-01 Epub Date: 2025-02-07 DOI: 10.1242/jcs.263438

Thomas Rauchenwald, Pia Benedikt-Kühnast, Sandra Eder, Gernot F Grabner, Sebastian Forstreiter, Michaela Lang, Roko Sango, Tobias Eisenberg, Thomas Rattei, Arvand Haschemi, Heimo Wolinski, Martina Schweiger

{"title":"Clearing the path for whole-mount labeling and quantification of neuron and vessel density in adipose tissue.","authors":"Thomas Rauchenwald, Pia Benedikt-Kühnast, Sandra Eder, Gernot F Grabner, Sebastian Forstreiter, Michaela Lang, Roko Sango, Tobias Eisenberg, Thomas Rattei, Arvand Haschemi, Heimo Wolinski, Martina Schweiger","doi":"10.1242/jcs.263438","DOIUrl":"10.1242/jcs.263438","url":null,"abstract":"White adipose tissue (WAT) comprises a plethora of cell types beyond adipocytes forming a regulatory network that ensures systemic energy homeostasis. Intertissue communication is facilitated by metabolites and signaling molecules that are spread by vasculature and nerves. Previous works have indicated that WAT responds to environmental cues by adapting the abundance of these 'communication routes'; however, the high intra-tissue heterogeneity questions the informative value of bulk or single-cell analyses and underscores the necessity of whole-mount imaging. The applicability of whole-mount WAT-imaging is currently limited by two factors - (1) methanol-based tissue clearing protocols restrict the usable antibody portfolio to methanol-resistant antibodies and (2) the vast amounts of data resulting from 3D imaging of whole-tissue samples require high computational expertise and advanced equipment. Here, we present a protocol for whole-mount WAT clearing, overcoming the constraints of antibody-methanol sensitivity. Additionally, we introduce TiNeQuant (for 'tissue network quantifier') a Fiji tool for automated 3D quantification of neuron or vascular network density, which we have made freely available. Given TiNeQuants versatility beyond WAT, it simplifies future efforts studying neuronal or vascular alterations in numerous pathologies.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0