Journal of Cell Biology最新文献_第3页

Myosin 15 participates in assembly and remodeling of the presynapse. 肌凝蛋白15参与突触前的组装和重塑。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2025-07-08 DOI: 10.1083/jcb.202305059

Astrid G Petzoldt,Marc J F Escher,Oriane Turrel,Niclas Gimber,Ina M Schedina,Sophie Walter,Torsten W B Götz,Marta Maglione,David Toppe,Tanja Matkovic-Rachid,Alexander Neumann,Janine Lützkendorf,Jan Schmoranzer,Martin Lehmann,Jörg Großhans,Stephan J Sigrist

{"title":"Myosin 15 participates in assembly and remodeling of the presynapse.","authors":"Astrid G Petzoldt,Marc J F Escher,Oriane Turrel,Niclas Gimber,Ina M Schedina,Sophie Walter,Torsten W B Götz,Marta Maglione,David Toppe,Tanja Matkovic-Rachid,Alexander Neumann,Janine Lützkendorf,Jan Schmoranzer,Martin Lehmann,Jörg Großhans,Stephan J Sigrist","doi":"10.1083/jcb.202305059","DOIUrl":"https://doi.org/10.1083/jcb.202305059","url":null,"abstract":"The assembly and remodeling of presynaptic specializations are of crucial importance for circuit development and adaptive behaviors. However, the mechanisms by which presynaptic material is locally distributed within synaptic terminals and across consuming active zones remain poorly understood. In this study, we identify the conserved unconventional class XV myosin, Myo15, an actin motor, as a novel regulator of presynaptic assembly and remodeling in Drosophila. Myo15 localizes to the local actin and microtubule network at synaptic terminals. Depletion of Myo15 resulted in smaller individual active zones, increased active zone density, and irregular terminal morphology, while its overexpression enlarged individual active zones and promoted synaptic terminal growth. Myo15 was found to modulate the actin meshwork, and deletion of its microtubule-binding MyTH4 domain rendered the protein nonfunctional. Furthermore, Myo15 was essential for presynaptic functional homeostatic plasticity and memory consolidation. These findings suggest that Myo15 plays a critical role in the assembly and remodeling of presynaptic active zones.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"47 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144578795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Pex30-dependent membrane contact sites maintain ER lipid homeostasis. pex30依赖的膜接触位点维持内质网脂质稳态。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-07-07 Epub Date: 2025-05-23 DOI: 10.1083/jcb.202409039

Joana Veríssimo Ferreira, Yara Ahmed, Tiaan Heunis, Aamna Jain, Errin Johnson, Markus Räschle, Robert Ernst, Stefano Vanni, Pedro Carvalho

{"title":"Pex30-dependent membrane contact sites maintain ER lipid homeostasis.","authors":"Joana Veríssimo Ferreira, Yara Ahmed, Tiaan Heunis, Aamna Jain, Errin Johnson, Markus Räschle, Robert Ernst, Stefano Vanni, Pedro Carvalho","doi":"10.1083/jcb.202409039","DOIUrl":"10.1083/jcb.202409039","url":null,"abstract":"In eukaryotic cells, communication between organelles and the coordination of their activities depend on membrane contact sites (MCS). How MCS are regulated under the dynamic cellular environment remains poorly understood. Here, we investigate how Pex30, a membrane protein localized to the endoplasmic reticulum (ER), regulates multiple MCS in budding yeast. We show that Pex30 is critical for the integrity of ER MCS with peroxisomes and vacuoles. This requires the dysferlin (DysF) domain on the Pex30 cytosolic tail. This domain binds to phosphatidic acid (PA) both in vitro and in silico, and it is important for normal PA metabolism in vivo. The DysF domain is evolutionarily conserved and may play a general role in PA homeostasis across eukaryotes. We further show that the ER-vacuole MCS requires a Pex30 C-terminal domain of unknown function and that its activity is controlled by phosphorylation in response to metabolic cues. These findings provide new insights into the dynamic nature of MCS and their coordination with cellular metabolism.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 7","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127381","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

Retinal ganglion cell migration and viability requires the kinase LKB1. 视网膜神经节细胞的迁移和生存需要LKB1激酶。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-07-07 Epub Date: 2025-06-11 DOI: 10.1083/jcb.202410023

Robert D Mackin, Ritika V Bhalla, Viktor Akhanov, Qudrat T Abdulwahab, Courtney A Burger, Melanie A Samuel

{"title":"Retinal ganglion cell migration and viability requires the kinase LKB1.","authors":"Robert D Mackin, Ritika V Bhalla, Viktor Akhanov, Qudrat T Abdulwahab, Courtney A Burger, Melanie A Samuel","doi":"10.1083/jcb.202410023","DOIUrl":"10.1083/jcb.202410023","url":null,"abstract":"The arrangement of neurons into ordered layers underlies circuit function in many nervous system regions. This is particularly true in the mammalian retina. Here, fate-committed retinal ganglion cells (RGCs) migrate from the apical to the inner retina, where they form connections that enable vision. The mechanisms that permit ganglion cell migration and whether distinct ganglion cell types use different migration modes are unknown. We show that the serine/threonine kinase LKB1 regulates ganglion cell migration and nuclear positioning. In the absence of LKB1, many ganglion cells remain in the apical retina. Misplaced cells show modified morphologies and display altered cytoskeletal proteins. Examination of RGC types revealed that LKB1 is specifically required to promote F-type RGC (F-RGC) migration. The failure of F-RGCs to migrate results in a significant F-RGC loss via increased cell death and microglia engulfment. Together, these results identify molecular determinates of ganglion cell migration and indicate that different ganglion cell types can use distinct programs to ensure their localization.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 7","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266327","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

Mitotic genome folding. 有丝分裂基因组折叠。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-07-07 Epub Date: 2025-06-10 DOI: 10.1083/jcb.202504075

Tatsuya Hirano

引用次数: 0

Calpains orchestrate secretion of annexin-containing microvesicles during membrane repair. 钙蛋白酶在膜修复过程中协调含膜联蛋白的微泡的分泌。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-07-07 Epub Date: 2025-05-16 DOI: 10.1083/jcb.202408159

Justin Krish Williams, Jordan Matthew Ngo, Abinayaa Murugupandiyan, Dorothy E Croall, H Criss Hartzell, Randy Schekman

{"title":"Calpains orchestrate secretion of annexin-containing microvesicles during membrane repair.","authors":"Justin Krish Williams, Jordan Matthew Ngo, Abinayaa Murugupandiyan, Dorothy E Croall, H Criss Hartzell, Randy Schekman","doi":"10.1083/jcb.202408159","DOIUrl":"10.1083/jcb.202408159","url":null,"abstract":"Microvesicles (MVs) are membrane-enclosed, plasma membrane-derived particles released by cells from all branches of life. MVs have utility as disease biomarkers and may participate in intercellular communication; however, physiological processes that induce their secretion are not known. Here, we isolate and characterize annexin-containing MVs and show that these vesicles are secreted in response to the calcium influx caused by membrane damage. The annexins in these vesicles are cleaved by calpains. After plasma membrane injury, cytoplasmic calcium-bound annexins are rapidly recruited to the plasma membrane and form a scab-like structure at the lesion. In a second phase, recruited annexins are cleaved by calpains-1/2, disabling membrane scabbing. Cleavage promotes annexin secretion within MVs. Our data support a new model of plasma membrane repair, where calpains relax annexin-membrane aggregates in the lesion repair scab, allowing secretion of damaged membrane and annexins as MVs. We anticipate that cells experiencing plasma membrane damage, including muscle and metastatic cancer cells, secrete these MVs at elevated levels.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 7","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078249","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

MTMR regulates KRAS function by controlling plasma membrane levels of phospholipids. MTMR通过控制质膜磷脂水平调节KRAS功能。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-07-07 Epub Date: 2025-05-02 DOI: 10.1083/jcb.202403126

Taylor E Lange, Ali Naji, Ransome van der Hoeven, Hong Liang, Yong Zhou, Gerald R V Hammond, John F Hancock, Kwang-Jin Cho

{"title":"MTMR regulates KRAS function by controlling plasma membrane levels of phospholipids.","authors":"Taylor E Lange, Ali Naji, Ransome van der Hoeven, Hong Liang, Yong Zhou, Gerald R V Hammond, John F Hancock, Kwang-Jin Cho","doi":"10.1083/jcb.202403126","DOIUrl":"https://doi.org/10.1083/jcb.202403126","url":null,"abstract":"KRAS, a small GTPase involved in cell proliferation and differentiation, frequently gains activating mutations in human cancers. For KRAS to function, it must bind the plasma membrane (PM) via interactions between its membrane anchor and phosphatidylserine (PtdSer). Therefore, depleting PM PtdSer abrogates KRAS PM binding and activity. From a genome-wide siRNA screen to identify genes regulating KRAS PM localization, we identified a set of phosphatidylinositol (PI) 3-phosphatases: myotubularin-related proteins (MTMR) 2, 3, 4, and 7. Here, we show that silencing MTMR 2/3/4/7 disrupts KRAS PM interactions by reducing PM PI 4-phosphate (PI4P) levels, thereby disrupting the localization and operation of ORP5, a lipid transfer protein maintaining PM PtdSer enrichment. Concomitantly, silencing MTMR 2/3/4/7 elevates PM PI3P levels while reducing PM and total PtdSer levels. We also observed MTMR 2/3/4/7 expression is interdependent. We propose that the PI 3-phosphatase activity of MTMR is required for generating PM PI, necessary for PM PI4P synthesis, promoting the PM localization of PtdSer and KRAS.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 7","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12047185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998594","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

Cargo adaptors use a handhold mechanism to engage with myosin V for organelle transport. 货物适配器使用手持机制与肌凝蛋白V进行细胞器运输。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-07-07 Epub Date: 2025-05-16 DOI: 10.1083/jcb.202408006

Hye Jee Hahn, Natalya Pashkova, Michael A Cianfrocco, Lois S Weisman

引用次数: 0

ALDH9A1 deficiency as a source of endogenous DNA damage that requires repair by the Fanconi anemia pathway. ALDH9A1缺乏作为内源性DNA损伤的来源，需要通过范可尼贫血途径修复。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-07-07 Epub Date: 2025-06-20 DOI: 10.1083/jcb.202407141

Moonjung Jung, Jungwoo Kim, Yeji Park, Isaac Ilyashov, Fan Yang, Haruna B Choijilsuren, Danielle Keahi, Jordan A Durmaz, Habin Bea, Audrey M Goldfarb, Mia D Stein, Claudia Wong, Ryan R White, Sunandini Sridhar, Raymond Noonan, Tom F Wiley, Thomas S Carroll, Francis P Lach, Sangmoo Jeong, Ileana C Miranda, Agata Smogorzewska

{"title":"ALDH9A1 deficiency as a source of endogenous DNA damage that requires repair by the Fanconi anemia pathway.","authors":"Moonjung Jung, Jungwoo Kim, Yeji Park, Isaac Ilyashov, Fan Yang, Haruna B Choijilsuren, Danielle Keahi, Jordan A Durmaz, Habin Bea, Audrey M Goldfarb, Mia D Stein, Claudia Wong, Ryan R White, Sunandini Sridhar, Raymond Noonan, Tom F Wiley, Thomas S Carroll, Francis P Lach, Sangmoo Jeong, Ileana C Miranda, Agata Smogorzewska","doi":"10.1083/jcb.202407141","DOIUrl":"10.1083/jcb.202407141","url":null,"abstract":"The Fanconi anemia (FA) DNA repair pathway is required for the repair of DNA interstrand cross-links (ICLs). ICLs are caused by genotoxins, such as chemotherapeutic agents or reactive aldehydes. Inappropriately repaired ICLs contribute to hematopoietic stem cell (HSC) failure and tumorigenesis. While endogenous acetaldehyde and formaldehyde are known to induce HSC failure and leukemia in FA patients, the effects of other toxic metabolites on FA pathogenesis have not been systematically investigated. Using a metabolism-focused CRISPR screen, we found a synthetically lethal interaction between ALDH9A1 and the deficiency of the FA pathway. Combined deficiency of ALDH9A1 and FANCD2 causes genomic instability, apoptosis, and decreased hematopoietic colony formation. Fanca-/-Aldh9a1-/- mice exhibited an increased incidence of ovarian tumors. A suppressor CRISPR screen revealed that the loss of ATP13A3, a polyamine transporter, resulted in improved survival of FANCD2-/-ALDH9A1-/- cells. These findings nominate high intracellular polyamines and the resulting 3-aminopropanal and acrolein as sources of endogenous DNA damage in patients with FA.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 7","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333223","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

Sphingolipid synthesis maintains nuclear membrane integrity and genome stability during cell division. 鞘脂合成在细胞分裂过程中维持核膜的完整性和基因组的稳定性。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2025-07-03 DOI: 10.1083/jcb.202407209

Sunyoung Hwang,William Russo,Jaylah Cormier,Jillian Johnson,Sara Martin,Marica Rosaria Ippolito,Sara Cordone,Rui Li,Lihua Julie Zhu,Stefano Santaguida,Eduardo M Torres

{"title":"Sphingolipid synthesis maintains nuclear membrane integrity and genome stability during cell division.","authors":"Sunyoung Hwang,William Russo,Jaylah Cormier,Jillian Johnson,Sara Martin,Marica Rosaria Ippolito,Sara Cordone,Rui Li,Lihua Julie Zhu,Stefano Santaguida,Eduardo M Torres","doi":"10.1083/jcb.202407209","DOIUrl":"https://doi.org/10.1083/jcb.202407209","url":null,"abstract":"Lipid synthesis must be precisely regulated to support membrane growth and organelle biogenesis during cell division, yet little is known about how this process is coordinated with other cell cycle events. Here, we show that de novo synthesis of sphingolipids during the S and G2 phases of the cell cycle is essential to increasing nuclear membranes. Indeed, the products of serine palmitoyltransferase (SPT), long-chain bases, localize to the nucleus and are integral components of nuclear membranes in yeast and human cells. Importantly, inhibition of SPT fails to induce cell cycle arrest, causing nuclear membrane collapse and loss of viability in yeast cells. In human cells, this causes abnormal nuclear morphology and genomic instability, evidenced by the increased incidence of nuclear blebs, micronuclei, anaphase bridges, and multipolar mitosis. These results indicate that dysregulated cell division under low sphingolipid availability can drive several disease-associated phenotypes, including aberrant nuclear morphologies and genomic instability.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"26 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Delta tubulin stabilizes male meiotic kinetochores and aids microtubule remodeling and fertility. 微管蛋白稳定雄性减数分裂着丝点，帮助微管重塑和生育。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2025-06-30 DOI: 10.1083/jcb.202412056

G Gemma Stathatos,D Jo Merriner,Anne E O'Connor,Jennifer Zenker,Jessica E M Dunleavy,Moira K O'Bryan

{"title":"Delta tubulin stabilizes male meiotic kinetochores and aids microtubule remodeling and fertility.","authors":"G Gemma Stathatos,D Jo Merriner,Anne E O'Connor,Jennifer Zenker,Jessica E M Dunleavy,Moira K O'Bryan","doi":"10.1083/jcb.202412056","DOIUrl":"https://doi.org/10.1083/jcb.202412056","url":null,"abstract":"Delta tubulin (TUBD1) is a noncanonical tubulin protein that has been linked to complex microtubule structures in somatic cell lines and unicellular species. Its role in mammals remains enigmatic; however, TUBD1 is enriched within mammalian male germ cells. Herein, we have defined new roles for TUBD1 during male germ cell development in vivo using a conditional knockout mouse model and shown that spermatogenesis in the absence of TUBD1 causes sterility. We show TUBD1 stabilizes kinetochores during male mouse meiosis, enabling meiotic progression, and that it is required for appropriate spindle polarity and cytokinesis. Subsequently, in haploid cells, TUBD1 works in partnership with the microtubule-severing enzymes KATNAL2 and KATNB1 to regulate manchette remodeling and shape the sperm head. Collectively, these findings reveal TUBD1 plays a key role in the formation and function of highly specialized microtubule structures in mammalian spermatogenesis. Advanced knowledge of TUBD1 may generate new insights into underlying causes of diseases associated with infertility or development.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"8 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144521463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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