Journal of Cell Biology最新文献_第7页

New editorial board members.

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-03-03 Epub Date: 2025-02-03 DOI: 10.1083/jcb.202501149

引用次数: 0

Single-molecule lipid biosensors mitigate inhibition of endogenous effector proteins.

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-03-03 Epub Date: 2025-02-11 DOI: 10.1083/jcb.202412026

Victoria L Holmes, Morgan M C Ricci, Claire C Weckerly, Michael Worcester, Gerald R V Hammond

{"title":"Single-molecule lipid biosensors mitigate inhibition of endogenous effector proteins.","authors":"Victoria L Holmes, Morgan M C Ricci, Claire C Weckerly, Michael Worcester, Gerald R V Hammond","doi":"10.1083/jcb.202412026","DOIUrl":"10.1083/jcb.202412026","url":null,"abstract":"Genetically encoded lipid biosensors uniquely provide real time, spatially resolved kinetic data for lipid dynamics in living cells. Despite clear strengths, these tools have significant drawbacks; most notably, lipid molecules bound to biosensors cannot engage with effectors, potentially inhibiting signaling. Here, we show that although PI 3-kinase (PI3K)-mediated activation of AKT is not significantly reduced in a cell population transfected with a PH-AKT1 PIP3/PI(3,4)P2 biosensor, single cells expressing PH-AKT at visible levels have reduced activation. Tagging endogenous AKT1 with neonGreen reveals its EGF-mediated translocation to the plasma membrane. Co-transfection with the PH-AKT1 or other PIP3 biosensors eliminates this translocation, despite robust recruitment of the biosensors. Inhibition is even observed with PI(3,4)P2-selective biosensor. However, expressing lipid biosensors at low levels, comparable with those of endogenous AKT, produced no such inhibition. Helpfully, these single-molecule biosensors revealed improved dynamic range and kinetic fidelity compared with overexpressed biosensor. This approach represents a noninvasive way to probe spatiotemporal dynamics of PI3K signaling in living cells.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11812570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

MYO18B promotes lysosomal exocytosis by facilitating focal adhesion maturation. MYO18B通过促进局灶黏附成熟来促进溶酶体胞吐。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-03-03 Epub Date: 2025-01-03 DOI: 10.1083/jcb.202407068

Wei-Wei Ren, Rebeca Kawahara, Kenichi G N Suzuki, Priya Dipta, Ganglong Yang, Morten Thaysen-Andersen, Morihisa Fujita

{"title":"MYO18B promotes lysosomal exocytosis by facilitating focal adhesion maturation.","authors":"Wei-Wei Ren, Rebeca Kawahara, Kenichi G N Suzuki, Priya Dipta, Ganglong Yang, Morten Thaysen-Andersen, Morihisa Fujita","doi":"10.1083/jcb.202407068","DOIUrl":"10.1083/jcb.202407068","url":null,"abstract":"Many cancer cells exhibit increased amounts of paucimannose glycans, which are truncated N-glycan structures rarely found in mammals. Paucimannosidic proteins are proposedly generated within lysosomes and exposed on the cell surface through a yet uncertain mechanism. In this study, we revealed that paucimannosidic proteins are produced by lysosomal glycosidases and secreted via lysosomal exocytosis. Interestingly, lysosomal exocytosis preferentially occurred in the vicinity of focal adhesions, protein complexes connecting the actin cytoskeleton to the extracellular matrix. Through genome-wide knockout screening, we identified that MYO18B, an actin crosslinker, is required for focal adhesion maturation, facilitating lysosomal exocytosis and the release of paucimannosidic lysosomal proteins to the extracellular milieu. Moreover, a mechanosensitive cation channel PIEZO1 locally activated at focal adhesions imports Ca2+ necessary for lysosome-plasma membrane fusion. Collectively, our study unveiled an intimate relationship between lysosomal exocytosis and focal adhesion, shedding light on the unexpected interplay between lysosomal activities and cellular mechanosensing.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Differential impacts of ribosomal protein haploinsufficiency on mitochondrial function. 核糖体蛋白单倍不全对线粒体功能的不同影响。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-03-03 Epub Date: 2025-01-09 DOI: 10.1083/jcb.202404084

Agustian Surya, Blythe Marie Bolton, Reed Rothe, Raquel Mejia-Trujillo, Amanda Leonita, Qiuxia Zhao, Alia Arya, Yue Liu, Rekha Rangan, Yasash Gorusu, Pamela Nguyen, Can Cenik, Elif Sarinay Cenik

{"title":"Differential impacts of ribosomal protein haploinsufficiency on mitochondrial function.","authors":"Agustian Surya, Blythe Marie Bolton, Reed Rothe, Raquel Mejia-Trujillo, Amanda Leonita, Qiuxia Zhao, Alia Arya, Yue Liu, Rekha Rangan, Yasash Gorusu, Pamela Nguyen, Can Cenik, Elif Sarinay Cenik","doi":"10.1083/jcb.202404084","DOIUrl":"10.1083/jcb.202404084","url":null,"abstract":"The interplay between ribosomal protein (RP) composition and mitochondrial function is essential for energy homeostasis. Balanced RP production optimizes protein synthesis while minimizing energy costs, but its impact on mitochondrial functionality remains unclear. Here, we investigated haploinsufficiency for RP genes (rps-10, rpl-5, rpl-33, and rps-23) in Caenorhabditis elegans and corresponding reductions in human lymphoblast cells. Significant mitochondrial morphological differences, upregulation of glutathione transferases, and SKN-1-dependent oxidative stress resistance were observed across mutants. Loss of a Datasingle rps-10 copy reduced mitochondrial activity, energy levels, and oxygen consumption, mirrored by similar reductions in mitochondrial activity and energy levels in lymphoblast cells with 50% lower RPS10 transcripts. Both systems exhibited altered translation efficiency (TE) of mitochondrial electron transport chain components, suggesting a conserved mechanism to adjust mitochondrial protein synthesis under ribosomal stress. Finally, mitochondrial membrane and cytosolic RPs showed significant RNA and TE covariation in lymphoblastoid cells, highlighting the interplay between protein synthesis machinery and mitochondrial energy production.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11716151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

A truncated isoform of Connexin43 caps actin to organize forward delivery of full-length Connexin43. 截短的异构体连接蛋白 43 能覆盖肌动蛋白，从而组织全长的连接蛋白 43 向前输送。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-03-03 Epub Date: 2024-12-31 DOI: 10.1083/jcb.202402112

Rachel Baum, Vu D Nguyen, Mario Maalouf, Daisuke Shimura, Miriam Waghalter, Sargis Srapyan, Qianru Jin, Lucas Kuzmanovich, Adelaide T Gaffney, Bridger R Bell, Shaohua Xiao, Joseph A Palatinus, André G Kléber, Elena E Grintsevich, TingTing Hong, Robin M Shaw

{"title":"A truncated isoform of Connexin43 caps actin to organize forward delivery of full-length Connexin43.","authors":"Rachel Baum, Vu D Nguyen, Mario Maalouf, Daisuke Shimura, Miriam Waghalter, Sargis Srapyan, Qianru Jin, Lucas Kuzmanovich, Adelaide T Gaffney, Bridger R Bell, Shaohua Xiao, Joseph A Palatinus, André G Kléber, Elena E Grintsevich, TingTing Hong, Robin M Shaw","doi":"10.1083/jcb.202402112","DOIUrl":"10.1083/jcb.202402112","url":null,"abstract":"While membrane proteins such as ion channels continuously turn over and require replacement, the mechanisms of specificity of efficient channel delivery to appropriate membrane subdomains remain poorly understood. GJA1-20k is a truncated Connexin43 (Cx43) isoform arising from translation initiating at an internal start codon within the same parent GJA1 mRNA and is requisite for full-length Cx43 trafficking to cell borders. GJA1-20k does not have a full transmembrane domain, and it is not known how GJA1-20k enables forward delivery of Cx43 hemichannels. Here, we report that a RPEL-like domain at the C terminus of GJA1-20k binds directly to actin and induces an actin phenotype similar to that of an actin-capping protein. Furthermore, GJA1-20k organizes actin within the cytoplasm to physically outline a forward delivery pathway for microtubule-based trafficking of Cx43 channels to follow. In conclusion, we find that the postal address of membrane-bound Cx43 channel delivery is defined by a separate protein encoded by the same mRNA of the channel itself.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Identification of the Polo-like kinase substrate required for homologous synapsis. 鉴定同源突触所需的Polo样激酶底物

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-03-03 Epub Date: 2024-12-16 DOI: 10.1083/jcb.202408092

Ariel L Gold, Matthew E Hurlock, Alicia M Guevara, Lilah Y Z Isenberg, Yumi Kim

{"title":"Identification of the Polo-like kinase substrate required for homologous synapsis.","authors":"Ariel L Gold, Matthew E Hurlock, Alicia M Guevara, Lilah Y Z Isenberg, Yumi Kim","doi":"10.1083/jcb.202408092","DOIUrl":"10.1083/jcb.202408092","url":null,"abstract":"The synaptonemal complex (SC) is a zipper-like protein structure that aligns homologous chromosome pairs and regulates recombination during meiosis. Despite its conserved appearance and function, how synapsis occurs between chromosome axes remains elusive. Here, we demonstrate that Polo-like kinases (PLKs) phosphorylate a single conserved residue in the disordered C-terminal tails of two paralogous SC subunits, SYP-5 and SYP-6, to establish an electrostatic interface between the SC central region and chromosome axes in C. elegans. While SYP-5/6 phosphorylation is dispensable for the ability of SC proteins to self-assemble, local phosphorylation by PLKs at the pairing center is crucial for SC elongation between homologous chromosome axes. Additionally, SYP-5/6 phosphorylation is essential for asymmetric SC disassembly and proper PLK-2 localization after crossover designation, which drives chromosome remodeling required for homolog separation during meiosis I. This work identifies a key regulatory mechanism by which localized PLK activity mediates the SC-axis interaction through phosphorylation of SYP-5/6, coupling synapsis initiation to homolog pairing.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

SARS-CoV-2 NSP3/4 control formation of replication organelle and recruitment of RNA polymerase NSP12. SARS-CoV-2 NSP3/4控制复制细胞器的形成和RNA聚合酶NSP12的募集。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-03-03 Epub Date: 2024-12-31 DOI: 10.1083/jcb.202306101

Jinping Yang, Buyun Tian, Pei Wang, Rongrong Chen, Ke Xiao, Xubing Long, Xinyue Zheng, Yun Zhu, Fei Sun, Yongxia Shi, Yaming Jiu, Wei Ji, Yanhong Xue, Tao Xu, Zonghong Li

{"title":"SARS-CoV-2 NSP3/4 control formation of replication organelle and recruitment of RNA polymerase NSP12.","authors":"Jinping Yang, Buyun Tian, Pei Wang, Rongrong Chen, Ke Xiao, Xubing Long, Xinyue Zheng, Yun Zhu, Fei Sun, Yongxia Shi, Yaming Jiu, Wei Ji, Yanhong Xue, Tao Xu, Zonghong Li","doi":"10.1083/jcb.202306101","DOIUrl":"10.1083/jcb.202306101","url":null,"abstract":"β-coronavirus rearranges the host cellular membranes to form double-membrane vesicles (DMVs) via NSP3/4, which anchor replication-transcription complexes (RTCs), thereby constituting the replication organelles (ROs). However, the impact of specific domains within NSP3/4 on DMV formation and RO assembly remains largely unknown. By using cryogenic-correlated light and electron microscopy (cryo-CLEM), we discovered that the N-terminal and C-terminal domains (NTD and CTD) of SARS-CoV-2 NSP3 are essential for DMV formation. Nevertheless, the CTD of NSP4 is not essential for DMV formation but regulates the DMV numbers. Additionally, the NTD of NSP3 is required for recruiting the RTC component to the cytosolic face of DMVs through direct interaction with NSP12 to assemble ROs. Furthermore, we observed that the size of NSP3/4-induced DMVs is smaller than virus-induced DMVs and established that RTC-mediated synthesis of double-stranded RNA (dsRNA) cargo plays a crucial role in determining DMV size. Collectively, our findings reveal that β-coronaviruses exploit the NSP3/4/12 axis to establish the viral ROs.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

α-Catenin force-sensitive binding and sequestration of LZTS2 leads to cytokinesis failure. α-Catenin力敏感结合和隔离LZTS2导致细胞分裂失败。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-03-03 Epub Date: 2025-01-09 DOI: 10.1083/jcb.202308124

Yuou Wang, Alex Yemelyanov, Christopher D Go, Sun K Kim, Jeanne M Quinn, Annette S Flozak, Phuong M Le, Shannon Liang, Anne-Claude Gingras, Mitsu Ikura, Noboru Ishiyama, Cara J Gottardi

{"title":"α-Catenin force-sensitive binding and sequestration of LZTS2 leads to cytokinesis failure.","authors":"Yuou Wang, Alex Yemelyanov, Christopher D Go, Sun K Kim, Jeanne M Quinn, Annette S Flozak, Phuong M Le, Shannon Liang, Anne-Claude Gingras, Mitsu Ikura, Noboru Ishiyama, Cara J Gottardi","doi":"10.1083/jcb.202308124","DOIUrl":"10.1083/jcb.202308124","url":null,"abstract":"Epithelial cells can become polyploid upon tissue injury, but mechanosensitive cues that trigger this state are poorly understood. Using an Madin Darby Canine Kidney (MDCK) cell knock-out/reconstitution system, we show that α-catenin mutants that alter force-sensitive binding to F-actin or middle (M)-domain promote cytokinesis failure and binucleation, particularly near epithelial wound-fronts. We identified Leucine Zipper Tumor Suppressor 2 (LZTS2), a factor previously implicated in abscission, as a conformation sensitive proximity partner of α-catenin. We show that LZTS2 enriches not only at midbody/intercellular bridges but also at apical adhering junctions. α-Catenin mutants with persistent M-domain opening show elevated junctional enrichment of LZTS2 compared with wild-type cells. LZTS2 knock-down leads to elevated rates of binucleation. These data implicate LZTS2 as a mechanosensitive effector of α-catenin that is critical for cytokinetic fidelity. This model rationalizes how persistent mechanoactivation of α-catenin may drive tension-induced polyploidization of epithelia after injury and suggests an underlying mechanism for how pathogenic α-catenin M-domain mutations drive macular dystrophy.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11716113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

TanGIBLE: A selective probe for evaluating hydrophobicity-exposed defective proteins in live cells. 一种选择性探针，用于评估活细胞中疏水性暴露的缺陷蛋白。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-03-03 Epub Date: 2025-01-15 DOI: 10.1083/jcb.202109010

Yasuyuki Iwasa, Sohtaroh Miyata, Takuya Tomita, Naoto Yokota, Maho Miyauchi, Ruka Mori, Shin Matsushita, Rigel Suzuki, Yasushi Saeki, Hiroyuki Kawahara

{"title":"TanGIBLE: A selective probe for evaluating hydrophobicity-exposed defective proteins in live cells.","authors":"Yasuyuki Iwasa, Sohtaroh Miyata, Takuya Tomita, Naoto Yokota, Maho Miyauchi, Ruka Mori, Shin Matsushita, Rigel Suzuki, Yasushi Saeki, Hiroyuki Kawahara","doi":"10.1083/jcb.202109010","DOIUrl":"10.1083/jcb.202109010","url":null,"abstract":"The accumulation of defective polypeptides in cells is a major cause of various diseases. However, probing defective proteins is difficult because no currently available method can retrieve unstable defective translational products in a soluble state. To overcome this issue, there is a need for a molecular device specific to structurally defective polypeptides. In this study, we developed an artificial protein architecture comprising tandemly aligned BAG6 Domain I, a minimum substrate recognition platform responsible for protein quality control. This tandem-aligned entity shows enhanced affinity not only for model defective polypeptides but also for endogenous polyubiquitinated proteins, which are sensitive to translational inhibition. Mass-spectrometry analysis with this probe enabled the identification of endogenous defective proteins, including orphaned subunits derived from multiprotein complexes and misassembled transmembrane proteins. This probe is also useful for the real-time visualization of protein foci derived from defective polypeptides in stressed cells. Therefore, this \"new molecular trap\" is a versatile tool for evaluating currently \"invisible\" pools of defective polypeptides as tangible entities.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 interkinetic envelope: A guardian or just a freeloader?

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-03-03 Epub Date: 2025-02-25 DOI: 10.1083/jcb.202501233

Griselda Velez-Aguilera, Verena Jantsch

引用次数: 0