{"title":"Discriminating motilities: Coordinating IFT with flagellar beating patterns.","authors":"Aline Araujo Alves, Philippe Bastin","doi":"10.1083/jcb.202407060","DOIUrl":"10.1083/jcb.202407060","url":null,"abstract":"<p><p>Intraflagellar transport has traditionally been studied in immobilized flagella. In this issue, Gray et al. (https://doi.org/10.1083/jcb.202401154) introduced a novel methodology for fast imaging in free-swimming Leishmania, revealing the impacts of flagellum immobilization on intraflagellar transport and its inverse correlation with cell swimming speed.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 9","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11307326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897533","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}
Kaiden M Power, Ken C Nguyen, Andriele Silva, Shaneen Singh, David H Hall, Christopher Rongo, Maureen M Barr
{"title":"NEKL-4 regulates microtubule stability and mitochondrial health in ciliated neurons.","authors":"Kaiden M Power, Ken C Nguyen, Andriele Silva, Shaneen Singh, David H Hall, Christopher Rongo, Maureen M Barr","doi":"10.1083/jcb.202402006","DOIUrl":"10.1083/jcb.202402006","url":null,"abstract":"<p><p>Ciliopathies are often caused by defects in the ciliary microtubule core. Glutamylation is abundant in cilia, and its dysregulation may contribute to ciliopathies and neurodegeneration. Mutation of the deglutamylase CCP1 causes infantile-onset neurodegeneration. In C. elegans, ccpp-1 loss causes age-related ciliary degradation that is suppressed by a mutation in the conserved NEK10 homolog nekl-4. NEKL-4 is absent from cilia, yet it negatively regulates ciliary stability via an unknown, glutamylation-independent mechanism. We show that NEKL-4 was mitochondria-associated. Additionally, nekl-4 mutants had longer mitochondria, a higher baseline mitochondrial oxidation state, and suppressed ccpp-1∆ mutant lifespan extension in response to oxidative stress. A kinase-dead nekl-4(KD) mutant ectopically localized to ccpp-1∆ cilia and rescued degenerating microtubule doublet B-tubules. A nondegradable nekl-4(PEST∆) mutant resembled the ccpp-1∆ mutant with dye-filling defects and B-tubule breaks. The nekl-4(PEST∆) Dyf phenotype was suppressed by mutation in the depolymerizing kinesin-8 KLP-13/KIF19A. We conclude that NEKL-4 influences ciliary stability by activating ciliary kinesins and promoting mitochondrial homeostasis.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 9","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11104396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065339","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}
{"title":"A three-way organelle junction controls PI(4)P metabolism and mitochondrial division.","authors":"York Posor, Volker Haucke","doi":"10.1083/jcb.202407125","DOIUrl":"10.1083/jcb.202407125","url":null,"abstract":"<p><p>Membrane contact sites (MCS) facilitate communication between organelles. Casler et al. (https://doi.org/10.1083/jcb.202308144) show that tripartite MCS between mitochondria, the endoplasmic reticulum (ER), and the plasma membrane (PM) regulate mitochondrial division and the distribution of phosphatidylinositol 4-phosphate [PI(4)P] on the PM.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 9","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11291957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855570","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}
Yanina D Alvarez, Marise van der Spuy, Jian Xiong Wang, Ivar Noordstra, Siew Zhuan Tan, Murron Carroll, Alpha S Yap, Olivier Serralbo, Melanie D White
{"title":"A Lifeact-EGFP quail for studying actin dynamics in vivo.","authors":"Yanina D Alvarez, Marise van der Spuy, Jian Xiong Wang, Ivar Noordstra, Siew Zhuan Tan, Murron Carroll, Alpha S Yap, Olivier Serralbo, Melanie D White","doi":"10.1083/jcb.202404066","DOIUrl":"10.1083/jcb.202404066","url":null,"abstract":"<p><p>Here, we report the generation of a transgenic Lifeact-EGFP quail line for the investigation of actin organization and dynamics during morphogenesis in vivo. This transgenic avian line allows for the high-resolution visualization of actin structures within the living embryo, from the subcellular filaments that guide cell shape to the supracellular assemblies that coordinate movements across tissues. The unique suitability of avian embryos to live imaging facilitates the investigation of previously intractable processes during embryogenesis. Using high-resolution live imaging approaches, we present the dynamic behaviors and morphologies of cellular protrusions in different tissue contexts. Furthermore, through the integration of live imaging with computational segmentation, we visualize cells undergoing apical constriction and large-scale actin structures such as multicellular rosettes within the neuroepithelium. These findings not only enhance our understanding of tissue morphogenesis but also demonstrate the utility of the Lifeact-EGFP transgenic quail as a new model system for live in vivo investigations of the actin cytoskeleton.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 9","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11194674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442743","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}
Weijing Yao, Yingcong Chen, Yi Zhang, Shu Zhong, Miaojuan Ye, Yuting Chen, Siyu Fan, Miao Ye, Huan Yang, Yixing Li, Choufei Wu, Mingzhu Fan, Shan Feng, Zhaoxiang He, Long Zhou, Liqin Zhang, Yigang Wang, Wei Liu, Jingjing Tong, Du Feng, Cong Yi
{"title":"Ca2+-triggered Atg11-Bmh1/2-Snf1 complex assembly initiates autophagy upon glucose starvation.","authors":"Weijing Yao, Yingcong Chen, Yi Zhang, Shu Zhong, Miaojuan Ye, Yuting Chen, Siyu Fan, Miao Ye, Huan Yang, Yixing Li, Choufei Wu, Mingzhu Fan, Shan Feng, Zhaoxiang He, Long Zhou, Liqin Zhang, Yigang Wang, Wei Liu, Jingjing Tong, Du Feng, Cong Yi","doi":"10.1083/jcb.202310049","DOIUrl":"10.1083/jcb.202310049","url":null,"abstract":"<p><p>Autophagy is essential for maintaining glucose homeostasis. However, the mechanism by which cells sense and respond to glucose starvation to induce autophagy remains incomplete. Here, we show that calcium serves as a fundamental triggering signal that connects environmental sensing to the formation of the autophagy initiation complex during glucose starvation. Mechanistically, glucose starvation instigates the release of vacuolar calcium into the cytoplasm, thus triggering the activation of Rck2 kinase. In turn, Rck2-mediated Atg11 phosphorylation enhances Atg11 interactions with Bmh1/2 bound to the Snf1-Sip1-Snf4 complex, leading to recruitment of vacuolar membrane-localized Snf1 to the PAS and subsequent Atg1 activation, thereby initiating autophagy. We also identified Glc7, a protein phosphatase-1, as a critical regulator of the association between Bmh1/2 and the Snf1 complex. We thus propose that calcium-triggered Atg11-Bmh1/2-Snf1 complex assembly initiates autophagy by controlling Snf1-mediated Atg1 activation in response to glucose starvation.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 9","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11232891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558842","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}
Farideh Sabeh, Xiao-Yan Li, Adam W Olson, Elliot Botvinick, Abhishek Kurup, Luis E Gimenez, Jung-Sun Cho, Stephen J Weiss
{"title":"Mmp14-dependent remodeling of the pericellular-dermal collagen interface governs fibroblast survival.","authors":"Farideh Sabeh, Xiao-Yan Li, Adam W Olson, Elliot Botvinick, Abhishek Kurup, Luis E Gimenez, Jung-Sun Cho, Stephen J Weiss","doi":"10.1083/jcb.202312091","DOIUrl":"10.1083/jcb.202312091","url":null,"abstract":"<p><p>Dermal fibroblasts deposit type I collagen, the dominant extracellular matrix molecule found in skin, during early postnatal development. Coincident with this biosynthetic program, fibroblasts proteolytically remodel pericellular collagen fibrils by mobilizing the membrane-anchored matrix metalloproteinase, Mmp14. Unexpectedly, dermal fibroblasts in Mmp14-/- mice commit to a large-scale apoptotic program that leaves skin tissues replete with dying cells. A requirement for Mmp14 in dermal fibroblast survival is recapitulated in vitro when cells are embedded within, but not cultured atop, three-dimensional hydrogels of crosslinked type I collagen. In the absence of Mmp14-dependent pericellular proteolysis, dermal fibroblasts fail to trigger β1 integrin activation and instead actuate a TGF-β1/phospho-JNK stress response that leads to apoptotic cell death in vitro as well as in vivo. Taken together, these studies identify Mmp14 as a requisite cell survival factor that maintains dermal fibroblast viability in postnatal dermal tissues.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 9","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11244150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590426","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}
Jason C Casler, Clare S Harper, Antoineen J White, Heidi L Anderson, Laura L Lackner
{"title":"Mitochondria-ER-PM contacts regulate mitochondrial division and PI(4)P distribution.","authors":"Jason C Casler, Clare S Harper, Antoineen J White, Heidi L Anderson, Laura L Lackner","doi":"10.1083/jcb.202308144","DOIUrl":"10.1083/jcb.202308144","url":null,"abstract":"<p><p>The mitochondria-ER-cortex anchor (MECA) forms a tripartite membrane contact site between mitochondria, the endoplasmic reticulum (ER), and the plasma membrane (PM). The core component of MECA, Num1, interacts with the PM and mitochondria via two distinct lipid-binding domains; however, the molecular mechanism by which Num1 interacts with the ER is unclear. Here, we demonstrate that Num1 contains a FFAT motif in its C-terminus that interacts with the integral ER membrane protein Scs2. While dispensable for Num1's functions in mitochondrial tethering and dynein anchoring, the FFAT motif is required for Num1's role in promoting mitochondrial division. Unexpectedly, we also reveal a novel function of MECA in regulating the distribution of phosphatidylinositol-4-phosphate (PI(4)P). Breaking Num1 association with any of the three membranes it tethers results in an accumulation of PI(4)P on the PM, likely via disrupting Sac1-mediated PI(4)P turnover. This work establishes MECA as an important regulatory hub that spatially organizes mitochondria, ER, and PM to coordinate crucial cellular functions.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 9","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11116812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086550","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}
Amol Ugale, Dhanlakshmi Shunmugam, Lokesh G Pimpale, Elisabeth Rebhan, Manuela Baccarini
{"title":"Signaling proteins in HSC fate determination are unequally segregated during asymmetric cell division.","authors":"Amol Ugale, Dhanlakshmi Shunmugam, Lokesh G Pimpale, Elisabeth Rebhan, Manuela Baccarini","doi":"10.1083/jcb.202310137","DOIUrl":"10.1083/jcb.202310137","url":null,"abstract":"<p><p>Hematopoietic stem cells (HSCs) continuously replenish mature blood cells with limited lifespans. To maintain the HSC compartment while ensuring output of differentiated cells, HSCs undergo asymmetric cell division (ACD), generating two daughter cells with different fates: one will proliferate and give rise to the differentiated cells' progeny, and one will return to quiescence to maintain the HSC compartment. A balance between MEK/ERK and mTORC1 pathways is needed to ensure HSC homeostasis. Here, we show that activation of these pathways is spatially segregated in premitotic HSCs and unequally inherited during ACD. A combination of genetic and chemical perturbations shows that an ERK-dependent mechanism determines the balance between pathways affecting polarity, proliferation, and metabolism, and thus determines the frequency of asymmetrically dividing HSCs. Our data identify druggable targets that modulate HSC fate determination at the level of asymmetric division.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 9","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11178505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317369","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}
{"title":"Leep2A and Leep2B function as a RasGAP complex to regulate macropinosome formation.","authors":"Xiaoting Chao, Yihong Yang, Weibin Gong, Songlin Zou, Hui Tu, Dong Li, Wei Feng, Huaqing Cai","doi":"10.1083/jcb.202401110","DOIUrl":"10.1083/jcb.202401110","url":null,"abstract":"<p><p>Macropinocytosis mediates the non-selective bulk uptake of extracellular fluid, enabling cells to survey the environment and obtain nutrients. A conserved set of signaling proteins orchestrates the actin dynamics that lead to membrane ruffling and macropinosome formation across various eukaryotic organisms. At the center of this signaling network are Ras GTPases, whose activation potently stimulates macropinocytosis. However, how Ras signaling is initiated and spatiotemporally regulated during macropinocytosis is not well understood. By using the model system Dictyostelium and a proteomics-based approach to identify regulators of macropinocytosis, we uncovered Leep2, consisting of Leep2A and Leep2B, as a RasGAP complex. The Leep2 complex specifically localizes to emerging macropinocytic cups and nascent macropinosomes, where it modulates macropinosome formation by regulating the activities of three Ras family small GTPases. Deletion or overexpression of the complex, as well as disruption or sustained activation of the target Ras GTPases, impairs macropinocytic activity. Our data reveal the critical role of fine-tuning Ras activity in directing macropinosome formation.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 9","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419272","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}
Xiao Li, Rico Gamuyao, Ming-Lun Wu, Woo Jung Cho, Sharon V King, R A Petersen, Daniel R Stabley, Caleb Lindow, Leslie K Climer, Abbas Shirinifard, Francesca Ferrara, Robert E Throm, Camenzind G Robinson, Yiwang Zhou, Alexandre F Carisey, Alison G Tebo, Chi-Lun Chang
{"title":"A fluorogenic complementation tool kit for interrogating lipid droplet-organelle interaction.","authors":"Xiao Li, Rico Gamuyao, Ming-Lun Wu, Woo Jung Cho, Sharon V King, R A Petersen, Daniel R Stabley, Caleb Lindow, Leslie K Climer, Abbas Shirinifard, Francesca Ferrara, Robert E Throm, Camenzind G Robinson, Yiwang Zhou, Alexandre F Carisey, Alison G Tebo, Chi-Lun Chang","doi":"10.1083/jcb.202311126","DOIUrl":"10.1083/jcb.202311126","url":null,"abstract":"<p><p>Contact sites between lipid droplets and other organelles are essential for cellular lipid and energy homeostasis upon metabolic demands. Detection of these contact sites at the nanometer scale over time in living cells is challenging. We developed a tool kit for detecting contact sites based on fluorogen-activated bimolecular complementation at CONtact sites, FABCON, using a reversible, low-affinity split fluorescent protein, splitFAST. FABCON labels contact sites with minimal perturbation to organelle interaction. Via FABCON, we quantitatively demonstrated that endoplasmic reticulum (ER)- and mitochondria (mito)-lipid droplet contact sites are dynamic foci in distinct metabolic conditions, such as during lipid droplet biogenesis and consumption. An automated analysis pipeline further classified individual contact sites into distinct subgroups based on size, likely reflecting differential regulation and function. Moreover, FABCON is generalizable to visualize a repertoire of organelle contact sites including ER-mito. Altogether, FABCON reveals insights into the dynamic regulation of lipid droplet-organelle contact sites and generates new hypotheses for further mechanistical interrogation during metabolic regulation.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 9","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141468235","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}