Journal of Cell Biology最新文献

Structure of the microtubule-anchoring factor NEDD1 bound to the γ-tubulin ring complex. 结合γ-微管蛋白环复合物的微管锚定因子NEDD1的结构。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-08-04 Epub Date: 2025-05-21 DOI: 10.1083/jcb.202410206

Hugo Muñoz-Hernández, Yixin Xu, Aitor Pellicer Camardiel, Daniel Zhang, Allen Xue, Amol Aher, Ellie Walker, Florina Marxer, Tarun M Kapoor, Michal Wieczorek

{"title":"Structure of the microtubule-anchoring factor NEDD1 bound to the γ-tubulin ring complex.","authors":"Hugo Muñoz-Hernández, Yixin Xu, Aitor Pellicer Camardiel, Daniel Zhang, Allen Xue, Amol Aher, Ellie Walker, Florina Marxer, Tarun M Kapoor, Michal Wieczorek","doi":"10.1083/jcb.202410206","DOIUrl":"10.1083/jcb.202410206","url":null,"abstract":"The γ-tubulin ring complex (γ-TuRC) is an essential multiprotein assembly that provides a template for microtubule nucleation. The γ-TuRC is recruited to microtubule-organizing centers (MTOCs) by the evolutionarily conserved attachment factor NEDD1. However, the structural basis of the NEDD1-γ-TuRC interaction is not known. Here, we report cryo-EM structures of NEDD1 bound to the human γ-TuRC in the absence or presence of the activating factor CDK5RAP2. We found that the C-terminus of NEDD1 forms a tetrameric α-helical assembly that contacts the lumen of the γ-TuRC cone and orients its microtubule-binding domain away from the complex. The structure of the γ-TuRC simultaneously bound to NEDD1 and CDK5RAP2 reveals that both factors can associate with the \"open\" conformation of the complex. Our results show that NEDD1 does not induce substantial conformational changes in the γ-TuRC but suggest that anchoring of γ-TuRC-capped microtubules by NEDD1 would be structurally compatible with the significant conformational changes experienced by the γ-TuRC during microtubule nucleation.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 8","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12094035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110599","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

Ecdysone regulates phagocytic cell fate of epithelial cells in developing Drosophila eggs. 蜕皮激素调节发育中的果蝇卵上皮细胞吞噬细胞的命运。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-08-04 Epub Date: 2025-05-28 DOI: 10.1083/jcb.202411073

Gaurab Ghosh, Devyan Das, Abhrajyoti Nandi, Souvik De, Sreeramaiah N Gangappa, Mohit Prasad

{"title":"Ecdysone regulates phagocytic cell fate of epithelial cells in developing Drosophila eggs.","authors":"Gaurab Ghosh, Devyan Das, Abhrajyoti Nandi, Souvik De, Sreeramaiah N Gangappa, Mohit Prasad","doi":"10.1083/jcb.202411073","DOIUrl":"10.1083/jcb.202411073","url":null,"abstract":"Acquisition of nonprofessional phagocytic cell fate plays an important role in sculpting functional metazoan organs and maintaining overall tissue homeostasis. Though physiologically highly relevant, how the normal epithelial cells acquire phagocytic fate is still mostly unclear. We have employed the Drosophila ovary model to demonstrate that the classical ecdysone signaling in the somatic epithelial follicle cells (AFCs) aids the removal of germline nurse cells (NCs) in late oogenesis. Our live-cell imaging data reveal a novel phenomenon wherein collective behavior of 4-5 AFCs is required for clearing a single NC. By employing classical genetics, molecular biology, and yeast one-hybrid assay, we demonstrate that ecdysone modulates the phagocytic disposition of AFCs at two levels. It regulates the epithelial-mesenchymal transition of the AFCs through Serpent and modulates the phagocytic behavior of the AFCs through Croquemort and Draper. Our data provide unprecedented novel molecular insights into how ecdysone signaling reprograms AFCs toward a phagocytic fate.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 8","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159236","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

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

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

The autophagy protein ATG-9 regulates lysosome function and integrity. 自噬蛋白ATG-9调节溶酶体的功能和完整性。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-06-02 Epub Date: 2025-04-09 DOI: 10.1083/jcb.202411092

Kangfu Peng, Guoxiu Zhao, Hongyu Zhao, Nobuo N Noda, Hong Zhang

引用次数: 0

A collagen IV fluorophore knock-in toolkit reveals trimer diversity in C. elegans basement membranes. 胶原IV荧光基团敲入工具包揭示了秀丽隐杆线虫基底膜的三聚体多样性。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-06-02 Epub Date: 2025-03-18 DOI: 10.1083/jcb.202412118

Sandhya Srinivasan, William Ramos-Lewis, Mychel R P T Morais, Qiuyi Chi, Adam W J Soh, Emily Williams, Rachel Lennon, David R Sherwood

{"title":"A collagen IV fluorophore knock-in toolkit reveals trimer diversity in C. elegans basement membranes.","authors":"Sandhya Srinivasan, William Ramos-Lewis, Mychel R P T Morais, Qiuyi Chi, Adam W J Soh, Emily Williams, Rachel Lennon, David R Sherwood","doi":"10.1083/jcb.202412118","DOIUrl":"10.1083/jcb.202412118","url":null,"abstract":"The type IV collagen triple helix, composed of three ⍺-chains, is a core basement membrane (BM) component that assembles into a network within BMs. Endogenous tagging of all ⍺-chains with genetically encoded fluorophores has remained elusive, limiting our understanding of this crucial BM component. Through genome editing, we show that the C termini of the C. elegans type IV collagen ⍺-chains EMB-9 and LET-2 can be fused to a variety of fluorophores to create a strain toolkit with wild-type health. Using quantitative imaging, our results suggest a preference for LET-2-LET-2-EMB-9 trimer construction, but also tissue-specific flexibility in trimers assembled driven by differences in ⍺-chain expression levels. By tagging emb-9 and let-2 mutants that model human Gould syndrome, a complex multitissue disorder, we further discover defects in extracellular accumulation and turnover that might help explain disease pathology. Together, our findings identify a permissive tagging site in C. elegans that will allow diverse studies on type IV collagen regulation and function in animals.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 6","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11917169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656812","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 postsynaptic density in excitatory synapses is composed of clustered, heterogeneous nanoblocks. 兴奋性突触的突触后密度是由聚集的、异质的纳米块组成的。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-06-02 Epub Date: 2025-03-27 DOI: 10.1083/jcb.202406133

Rong Sun, James P Allen, Zhuqing Mao, Liana Wilson, Mariam Haider, Baris Alten, Zimeng Zhou, Xinyi Wang, Qiangjun Zhou

{"title":"The postsynaptic density in excitatory synapses is composed of clustered, heterogeneous nanoblocks.","authors":"Rong Sun, James P Allen, Zhuqing Mao, Liana Wilson, Mariam Haider, Baris Alten, Zimeng Zhou, Xinyi Wang, Qiangjun Zhou","doi":"10.1083/jcb.202406133","DOIUrl":"10.1083/jcb.202406133","url":null,"abstract":"The nanoscale organization of proteins within synapses is critical for maintaining and regulating synaptic transmission and plasticity. Here, we used cryo-electron tomography (cryo-ET) to directly visualize the three-dimensional architecture and supramolecular organization of postsynaptic components in both synaptosomes and synapses from cultured neurons. Cryo-ET revealed that postsynaptic density (PSD) is composed of membrane-associated nanoblocks of various sizes. Subtomogram averaging from synaptosomes showed two types (type A and B) of postsynaptic receptor-like particles at resolutions of 24 and 26 Å, respectively. Furthermore, our analysis suggested that potential presynaptic release sites are closer to nanoblocks with type A/B receptor-like particles than to nanoblocks without type A/B receptor-like particles. The results of this study provide a more comprehensive understanding of synaptic ultrastructure and suggest that PSD is composed of clustering of various nanoblocks. These nanoblocks are heterogeneous in size, assembly, and distribution, which likely contribute to the dynamic nature of PSD in modulating synaptic strength.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 6","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719375","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 Abelson kinase and the Nedd4 family E3 ligases co-regulate Notch trafficking to limit signaling. Abelson激酶和Nedd4家族E3连接酶共同调节Notch转运以限制信号传导。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-06-02 Epub Date: 2025-04-04 DOI: 10.1083/jcb.202407066

Julio Miranda-Alban, Nicelio Sanchez-Luege, Fernando M Valbuena, Chyan Rangel, Ilaria Rebay

{"title":"The Abelson kinase and the Nedd4 family E3 ligases co-regulate Notch trafficking to limit signaling.","authors":"Julio Miranda-Alban, Nicelio Sanchez-Luege, Fernando M Valbuena, Chyan Rangel, Ilaria Rebay","doi":"10.1083/jcb.202407066","DOIUrl":"10.1083/jcb.202407066","url":null,"abstract":"Precise output from the conserved Notch signaling pathway governs a plethora of cellular processes and developmental transitions. Unlike other pathways that use a cytoplasmic relay, the Notch cell surface receptor transduces signaling directly to the nucleus, with endocytic trafficking providing critical regulatory nodes. Here we report that the cytoplasmic tyrosine kinase Abelson (Abl) facilitates Notch internalization into late endosomes/multivesicular bodies (LEs), thereby limiting signaling output in both ligand-dependent and -independent contexts. Abl phosphorylates the PPxY motif within Notch, a molecular target for its degradation via Nedd4 family ubiquitin ligases. We show that Su(dx), a family member, mediates the Abl-directed LE regulation of Notch via the PPxY, while another family member, Nedd4Lo, contributes to Notch internalization into LEs through both PPxY-dependent and -independent mechanisms. Our findings demonstrate how a network of posttranslational modifiers converging at LEs cooperatively modulates Notch signaling to ensure the precision and robustness of its cellular and developmental functions.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 6","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780020","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