The Journal of Cell Biology最新文献

筛选
英文 中文
Spatiotemporal control of actomyosin contractility by MRCKβ signaling drives phagocytosis. MRCKβ信号传导对肌动球蛋白收缩性的时空调控驱动吞噬作用。
IF 7.8
The Journal of Cell Biology Pub Date : 2022-11-07 Epub Date: 2022-09-19 DOI: 10.1083/jcb.202012042
Ceniz Zihni, Anastasios Georgiadis, Conor M Ramsden, Elena Sanchez-Heras, Alexis J Haas, Britta Nommiste, Olha Semenyuk, James W B Bainbridge, Peter J Coffey, Alexander J Smith, Robin R Ali, Maria S Balda, Karl Matter
{"title":"Spatiotemporal control of actomyosin contractility by MRCKβ signaling drives phagocytosis.","authors":"Ceniz Zihni,&nbsp;Anastasios Georgiadis,&nbsp;Conor M Ramsden,&nbsp;Elena Sanchez-Heras,&nbsp;Alexis J Haas,&nbsp;Britta Nommiste,&nbsp;Olha Semenyuk,&nbsp;James W B Bainbridge,&nbsp;Peter J Coffey,&nbsp;Alexander J Smith,&nbsp;Robin R Ali,&nbsp;Maria S Balda,&nbsp;Karl Matter","doi":"10.1083/jcb.202012042","DOIUrl":"https://doi.org/10.1083/jcb.202012042","url":null,"abstract":"<p><p>Phagocytosis requires actin dynamics, but whether actomyosin contractility plays a role in this morphodynamic process is unclear. Here, we show that in the retinal pigment epithelium (RPE), particle binding to Mer Tyrosine Kinase (MerTK), a widely expressed phagocytic receptor, stimulates phosphorylation of the Cdc42 GEF Dbl3, triggering activation of MRCKβ/myosin-II and its coeffector N-WASP, membrane deformation, and cup formation. Continued MRCKβ/myosin-II activity then drives recruitment of a mechanosensing bridge, enabling cytoskeletal force transmission, cup closure, and particle internalization. In vivo, MRCKβ is essential for RPE phagocytosis and retinal integrity. MerTK-independent activation of MRCKβ signaling by a phosphomimetic Dbl3 mutant rescues phagocytosis in retinitis pigmentosa RPE cells lacking functional MerTK. MRCKβ is also required for efficient particle translocation from the cortex into the cell body in Fc receptor-mediated phagocytosis. Thus, conserved MRCKβ signaling at the cortex controls spatiotemporal regulation of actomyosin contractility to guide distinct phases of phagocytosis in the RPE and represents the principle phagocytic effector pathway downstream of MerTK.</p>","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2022-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9485704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40366493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Vav independently regulates synaptic growth and plasticity through distinct actin-based processes. Vav通过不同的基于肌动蛋白的过程独立调节突触的生长和可塑性。
IF 7.8
The Journal of Cell Biology Pub Date : 2022-10-03 Epub Date: 2022-08-17 DOI: 10.1083/jcb.202203048
Hyun Gwan Park, Yeongjin David Kim, Eunsang Cho, Ting-Yi Lu, Chi-Kuang Yao, Jihye Lee, Seungbok Lee
{"title":"Vav independently regulates synaptic growth and plasticity through distinct actin-based processes.","authors":"Hyun Gwan Park,&nbsp;Yeongjin David Kim,&nbsp;Eunsang Cho,&nbsp;Ting-Yi Lu,&nbsp;Chi-Kuang Yao,&nbsp;Jihye Lee,&nbsp;Seungbok Lee","doi":"10.1083/jcb.202203048","DOIUrl":"https://doi.org/10.1083/jcb.202203048","url":null,"abstract":"<p><p>Modulation of presynaptic actin dynamics is fundamental to synaptic growth and functional plasticity; yet the underlying molecular and cellular mechanisms remain largely unknown. At Drosophila NMJs, the presynaptic Rac1-SCAR pathway mediates BMP-induced receptor macropinocytosis to inhibit BMP growth signaling. Here, we show that the Rho-type GEF Vav acts upstream of Rac1 to inhibit synaptic growth through macropinocytosis. We also present evidence that Vav-Rac1-SCAR signaling has additional roles in tetanus-induced synaptic plasticity. Presynaptic inactivation of Vav signaling pathway components, but not regulators of macropinocytosis, impairs post-tetanic potentiation (PTP) and enhances synaptic depression depending on external Ca2+ concentration. Interfering with the Vav-Rac1-SCAR pathway also impairs mobilization of reserve pool (RP) vesicles required for tetanus-induced synaptic plasticity. Finally, treatment with an F-actin-stabilizing drug completely restores RP mobilization and plasticity defects in Vav mutants. We propose that actin-regulatory Vav-Rac1-SCAR signaling independently regulates structural and functional presynaptic plasticity by driving macropinocytosis and RP mobilization, respectively.</p>","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2022-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9388202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40620113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Tensin3 interaction with talin drives the formation of fibronectin-associated fibrillar adhesions. Tensin3与talin相互作用驱动纤维连接蛋白相关纤维粘连的形成。
IF 7.8
The Journal of Cell Biology Pub Date : 2022-10-03 Epub Date: 2022-09-08 DOI: 10.1083/jcb.202107022
Paul Atherton, Rafaella Konstantinou, Suat Peng Neo, Emily Wang, Eleonora Balloi, Marina Ptushkina, Hayley Bennett, Kath Clark, Jayantha Gunaratne, David Critchley, Igor Barsukov, Edward Manser, Christoph Ballestrem
{"title":"Tensin3 interaction with talin drives the formation of fibronectin-associated fibrillar adhesions.","authors":"Paul Atherton,&nbsp;Rafaella Konstantinou,&nbsp;Suat Peng Neo,&nbsp;Emily Wang,&nbsp;Eleonora Balloi,&nbsp;Marina Ptushkina,&nbsp;Hayley Bennett,&nbsp;Kath Clark,&nbsp;Jayantha Gunaratne,&nbsp;David Critchley,&nbsp;Igor Barsukov,&nbsp;Edward Manser,&nbsp;Christoph Ballestrem","doi":"10.1083/jcb.202107022","DOIUrl":"https://doi.org/10.1083/jcb.202107022","url":null,"abstract":"<p><p>The formation of healthy tissue involves continuous remodeling of the extracellular matrix (ECM). Whilst it is known that this requires integrin-associated cell-ECM adhesion sites (CMAs) and actomyosin-mediated forces, the underlying mechanisms remain unclear. Here, we examine how tensin3 contributes to the formation of fibrillar adhesions (FBs) and fibronectin fibrillogenesis. Using BioID mass spectrometry and a mitochondrial targeting assay, we establish that tensin3 associates with the mechanosensors such as talin and vinculin. We show that the talin R11 rod domain binds directly to a helical motif within the central intrinsically disordered region (IDR) of tensin3, whilst vinculin binds indirectly to tensin3 via talin. Using CRISPR knock-out cells in combination with defined tensin3 mutations, we show (i) that tensin3 is critical for the formation of α5β1-integrin FBs and for fibronectin fibrillogenesis, and (ii) the talin/tensin3 interaction drives this process, with vinculin acting to potentiate it.</p>","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2022-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9462884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33449585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
NCOA4 drives ferritin phase separation to facilitate macroferritinophagy and microferritinophagy. NCOA4驱动铁蛋白相分离,促进大铁蛋白自噬和微铁蛋白自噬。
IF 7.8
The Journal of Cell Biology Pub Date : 2022-10-03 Epub Date: 2022-09-06 DOI: 10.1083/jcb.202203102
Tomoko Ohshima, Hayashi Yamamoto, Yuriko Sakamaki, Chieko Saito, Noboru Mizushima
{"title":"NCOA4 drives ferritin phase separation to facilitate macroferritinophagy and microferritinophagy.","authors":"Tomoko Ohshima,&nbsp;Hayashi Yamamoto,&nbsp;Yuriko Sakamaki,&nbsp;Chieko Saito,&nbsp;Noboru Mizushima","doi":"10.1083/jcb.202203102","DOIUrl":"https://doi.org/10.1083/jcb.202203102","url":null,"abstract":"<p><p>A ferritin particle consists of 24 ferritin proteins (FTH1 and FTL) and stores iron ions within it. During iron deficiency, ferritin particles are transported to lysosomes to release iron ions. Two transport pathways have been reported: macroautophagy and ESCRT-dependent endosomal microautophagy. Although the membrane dynamics of these pathways differ, both require NCOA4, which is thought to be an autophagy receptor for ferritin. However, it is unclear whether NCOA4 only acts as an autophagy receptor in ferritin degradation. Here, we found that ferritin particles form liquid-like condensates in a NCOA4-dependent manner. Homodimerization of NCOA4 and interaction between FTH1 and NCOA4 (i.e., multivalent interactions between ferritin particles and NCOA4) were required for the formation of ferritin condensates. Disruption of these interactions impaired ferritin degradation. Time-lapse imaging and three-dimensional correlative light and electron microscopy revealed that these ferritin-NCOA4 condensates were directly engulfed by autophagosomes and endosomes. In contrast, TAX1BP1 was not required for the formation of ferritin-NCOA4 condensates but was required for their incorporation into autophagosomes and endosomes. These results suggest that NCOA4 acts not only as a canonical autophagy receptor but also as a driver to form ferritin condensates to facilitate the degradation of these condensates by macroautophagy (i.e., macroferritinophagy) and endosomal microautophagy (i.e., microferritinophagy).</p>","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2022-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9452830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40352411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 16
DeepContact: High-throughput quantification of membrane contact sites based on electron microscopy imaging. 深度接触:基于电子显微镜成像的膜接触部位的高通量定量。
IF 7.8
The Journal of Cell Biology Pub Date : 2022-09-05 Epub Date: 2022-08-05 DOI: 10.1083/jcb.202106190
Liqing Liu, Shuxin Yang, Yang Liu, Xixia Li, Junjie Hu, Li Xiao, Tao Xu
{"title":"DeepContact: High-throughput quantification of membrane contact sites based on electron microscopy imaging.","authors":"Liqing Liu,&nbsp;Shuxin Yang,&nbsp;Yang Liu,&nbsp;Xixia Li,&nbsp;Junjie Hu,&nbsp;Li Xiao,&nbsp;Tao Xu","doi":"10.1083/jcb.202106190","DOIUrl":"https://doi.org/10.1083/jcb.202106190","url":null,"abstract":"<p><p>Membrane contact site (MCS)-mediated organelle interactions play essential roles in the cell. Quantitative analysis of MCSs reveals vital clues for cellular responses under various physiological and pathological conditions. However, an efficient tool is lacking. Here, we developed DeepContact, a deep-learning protocol for optimizing organelle segmentation and contact analysis based on label-free EM. DeepContact presents high efficiency and flexibility in interactive visualizations, accommodating new morphologies of organelles and recognizing contacts in versatile width ranges, which enables statistical analysis of various types of MCSs in multiple systems. DeepContact profiled previously unidentified coordinative rearrangements of MCS types in cultured cells with combined nutritional conditions. DeepContact also unveiled a subtle wave of ER-mitochondrial entanglement in Sertoli cells during the seminiferous epithelial cycle, indicating its potential in bridging MCS dynamics to physiological and pathological processes.</p>","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2022-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9361564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40586725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
An integrin axis induces IFN-β production in plasmacytoid dendritic cells. 整合素轴诱导浆细胞样树突状细胞产生IFN-β。
IF 7.8
The Journal of Cell Biology Pub Date : 2022-09-05 Epub Date: 2022-07-25 DOI: 10.1083/jcb.202102055
Davina Camargo Madeira Simoes, Nikolaos Paschalidis, Evangelia Kourepini, Vily Panoutsakopoulou
{"title":"An integrin axis induces IFN-β production in plasmacytoid dendritic cells.","authors":"Davina Camargo Madeira Simoes,&nbsp;Nikolaos Paschalidis,&nbsp;Evangelia Kourepini,&nbsp;Vily Panoutsakopoulou","doi":"10.1083/jcb.202102055","DOIUrl":"https://doi.org/10.1083/jcb.202102055","url":null,"abstract":"<p><p>Type I interferon (IFN) production by plasmacytoid dendritic cells (pDCs) has been mainly studied in the context of Toll-like receptor (TLR) activation. In the current report, we reveal that, in the absence of TLR activation, the integrin-binding SLAYGLR motif of secreted osteopontin (sOpn) induces IFN-β production in murine pDCs. This process is mediated by α4β1 integrin, indicating that integrin triggering may act as a subtle danger signal leading to IFN-β induction. The SLAYGLR-mediated α4 integrin/IFN-β axis is MyD88 independent and operates via a PI3K/mTOR/IRF3 pathway. Consequently, SLAYGLR-treated pDCs produce increased levels of type I IFNs following TLR stimulation. Intratumoral administration of SLAYGLR induces accumulation of IFN-β-expressing pDCs and efficiently suppresses melanoma tumor growth. In this process, pDCs are crucial. Finally, SLAYGLR enhances pDC development from bone marrow progenitors. These findings open new questions on the roles of sOpn and integrin α4 during homeostasis and inflammation. The newly identified integrin/IFN-β axis may be implicated in a wide array of immune responses.</p>","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2022-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40633544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Mechanistic basis for Sgo1-mediated centromere localization and function of the CPC. sgo1介导的着丝粒定位和CPC功能的机制基础。
The Journal of Cell Biology Pub Date : 2022-08-01 Epub Date: 2022-07-01 DOI: 10.1083/jcb.202108156
Maria Alba Abad, Tanmay Gupta, Michael A Hadders, Amanda Meppelink, J Pepijn Wopken, Elizabeth Blackburn, Juan Zou, Anjitha Gireesh, Lana Buzuk, David A Kelly, Toni McHugh, Juri Rappsilber, Susanne M A Lens, A Arockia Jeyaprakash
{"title":"Mechanistic basis for Sgo1-mediated centromere localization and function of the CPC.","authors":"Maria Alba Abad, Tanmay Gupta, Michael A Hadders, Amanda Meppelink, J Pepijn Wopken, Elizabeth Blackburn, Juan Zou, Anjitha Gireesh, Lana Buzuk, David A Kelly, Toni McHugh, Juri Rappsilber, Susanne M A Lens, A Arockia Jeyaprakash","doi":"10.1083/jcb.202108156","DOIUrl":"10.1083/jcb.202108156","url":null,"abstract":"<p><p>Centromere association of the chromosomal passenger complex (CPC; Borealin-Survivin-INCENP-Aurora B) and Sgo1 is crucial for chromosome biorientation, a process essential for error-free chromosome segregation. Phosphorylated histone H3 Thr3 (H3T3ph; directly recognized by Survivin) and histone H2A Thr120 (H2AT120ph; indirectly recognized via Sgo1), together with CPC's intrinsic nucleosome-binding ability, facilitate CPC centromere recruitment. However, the molecular basis for CPC-Sgo1 binding and how their physical interaction influences CPC centromere localization are lacking. Here, using an integrative structure-function approach, we show that the \"histone H3-like\" Sgo1 N-terminal tail-Survivin BIR domain interaction acts as a hotspot essential for CPC-Sgo1 assembly, while downstream Sgo1 residues and Borealin contribute for high-affinity binding. Disrupting Sgo1-Survivin interaction abolished CPC-Sgo1 assembly and perturbed CPC centromere localization and function. Our findings reveal that Sgo1 and H3T3ph use the same surface on Survivin to bind CPC. Hence, it is likely that these interactions take place in a spatiotemporally restricted manner, providing a rationale for the Sgo1-mediated \"kinetochore-proximal\" CPC centromere pool.</p>","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9253516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40463044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Regulation of the COPII secretory machinery via focal adhesions and extracellular matrix signaling. 通过局灶黏附和细胞外基质信号传导调节COPII分泌机制。
IF 7.8
The Journal of Cell Biology Pub Date : 2022-08-01 Epub Date: 2022-07-13 DOI: 10.1083/jcb.202110081
Juan Jung, Muzamil Majid Khan, Jonathan Landry, Aliaksandr Halavatyi, Pedro Machado, Miriam Reiss, Rainer Pepperkok
{"title":"Regulation of the COPII secretory machinery via focal adhesions and extracellular matrix signaling.","authors":"Juan Jung,&nbsp;Muzamil Majid Khan,&nbsp;Jonathan Landry,&nbsp;Aliaksandr Halavatyi,&nbsp;Pedro Machado,&nbsp;Miriam Reiss,&nbsp;Rainer Pepperkok","doi":"10.1083/jcb.202110081","DOIUrl":"https://doi.org/10.1083/jcb.202110081","url":null,"abstract":"<p><p>Proteins that enter the secretory pathway are transported from their place of synthesis in the endoplasmic reticulum to the Golgi complex by COPII-coated carriers. The networks of proteins that regulate these components in response to extracellular cues have remained largely elusive. Using high-throughput microscopy, we comprehensively screened 378 cytoskeleton-associated and related proteins for their functional interaction with the coat protein complex II (COPII) components SEC23A and SEC23B. Among these, we identified a group of proteins associated with focal adhesions (FERMT2, MACF1, MAPK8IP2, NGEF, PIK3CA, and ROCK1) that led to the downregulation of SEC23A when depleted by siRNA. Changes in focal adhesions induced by plating cells on ECM also led to the downregulation of SEC23A and decreases in VSVG transport from ER to Golgi. Both the expression of SEC23A and the transport defect could be rescued by treatment with a focal adhesion kinase inhibitor. Altogether, our results identify a network of cytoskeleton-associated proteins connecting focal adhesions and ECM-related signaling with the gene expression of the COPII secretory machinery and trafficking.</p>","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40518014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Coronin 1C restricts endosomal branched actin to organize ER contact and endosome fission. 冠状蛋白1C限制核内体分支肌动蛋白组织内质网接触和核内体裂变。
IF 7.8
The Journal of Cell Biology Pub Date : 2022-08-01 Epub Date: 2022-07-08 DOI: 10.1083/jcb.202110089
Jonathan F Striepen, Gia K Voeltz
{"title":"Coronin 1C restricts endosomal branched actin to organize ER contact and endosome fission.","authors":"Jonathan F Striepen,&nbsp;Gia K Voeltz","doi":"10.1083/jcb.202110089","DOIUrl":"https://doi.org/10.1083/jcb.202110089","url":null,"abstract":"<p><p>ER contact sites define the position of endosome bud fission during actin-dependent cargo sorting. Disrupting endosomal actin structures prevents retrograde cargo movement; however, how actin affects ER contact site formation and endosome fission is not known. Here we show that in contrast with the WASH complex, actin, its nucleator ARP2/3, and COR1C form a contained structure at the bud neck that defines the site of bud fission. We found that actin confinement is facilitated by type I coronins. Depletion of type I coronins allows actin to extend along the length of the bud in an ARP2/3-dependent manner. We demonstrate that extension of branched actin prevents ER recruitment and stalls buds before fission. Finally, our structure-function studies show that the COR1C's coiled-coil domain is sufficient to restore actin confinement, ER recruitment, and endosome fission. Together, our data reveal how the dynamics of endosomal actin and activity of actin regulators organize ER-associated bud fission.</p>","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40581872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
A two-step search and run response to gradients shapes leukocyte navigation in vivo. 两步搜索和运行响应梯度形状白细胞导航在体内。
IF 7.8
The Journal of Cell Biology Pub Date : 2022-08-01 Epub Date: 2022-06-22 DOI: 10.1083/jcb.202103207
Antonios Georgantzoglou, Hugo Poplimont, Hazel A Walker, Tim Lämmermann, Milka Sarris
{"title":"A two-step search and run response to gradients shapes leukocyte navigation in vivo.","authors":"Antonios Georgantzoglou,&nbsp;Hugo Poplimont,&nbsp;Hazel A Walker,&nbsp;Tim Lämmermann,&nbsp;Milka Sarris","doi":"10.1083/jcb.202103207","DOIUrl":"https://doi.org/10.1083/jcb.202103207","url":null,"abstract":"<p><p>Migrating cells must interpret chemical gradients to guide themselves within tissues. A long-held principle is that gradients guide cells via reorientation of leading-edge protrusions. However, recent evidence indicates that protrusions can be dispensable for locomotion in some contexts, raising questions about how cells interpret endogenous gradients in vivo and whether other mechanisms are involved. Using laser wound assays in zebrafish to elicit acute endogenous gradients and quantitative analyses, we demonstrate a two-stage process for leukocyte chemotaxis in vivo: first a \"search\" phase, with stimulation of actin networks at the leading edge, cell deceleration, and turning. This is followed by a \"run\" phase, with fast actin flows, cell acceleration, and persistence. When actin dynamics are perturbed, cells fail to resolve the gradient, suggesting that pure spatial sensing of the gradient is insufficient for navigation. Our data suggest that cell contractility and actin flows provide memory for temporal sensing, while expansion of the leading edge serves to enhance gradient sampling.</p>","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40178235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 8
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信