Journal of Cell Biology最新文献

Arc controls organ architecture through modulation of Crb and MyoII. Arc通过调节Crb和MyoII来控制器官结构。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-09-01 Epub Date: 2025-06-12 DOI: 10.1083/jcb.202409078

Ji Hoon Kim, Rika Maruyama, Kwon Kim, Devin A Vertrees, Parama Paul, Kyla Britson, Nathaniel R Laughner, Deborah J Andrew

{"title":"Arc controls organ architecture through modulation of Crb and MyoII.","authors":"Ji Hoon Kim, Rika Maruyama, Kwon Kim, Devin A Vertrees, Parama Paul, Kyla Britson, Nathaniel R Laughner, Deborah J Andrew","doi":"10.1083/jcb.202409078","DOIUrl":"10.1083/jcb.202409078","url":null,"abstract":"Precise orchestration of morphogenetic processes generates organs that are optimally positioned and the right size and shape to fit and maximize functionality. Here, we show that Arc, a large apical membrane-associated PDZ domain-containing protein, works through the apical determinant Crumbs to limit non-muscle myosin II (MyoII) activity during tissue invagination in the Drosophila salivary gland (SG). We show that loss of Arc, attenuation of Crumbs, and increased activation of MyoII leads to the simultaneous internalization of more precursor cells than normal. Consequently, mature SGs are shorter with more cells surrounding the lumen all along the tube. Correspondingly, overexpression of Arc or SG-specific knockdown of MyoII leads to longer SGs with fewer cells surrounding the lumen. Our findings support a model wherein plasma membrane (PM)-associated Crumbs stabilizes cellular junctions by limiting apical pools of activated MyoII and countering the destabilizing effects of MyoII at the PM, limiting how many cells internalize at any given time, shaping final tube geometry.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 9","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274959","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

Visualizing nuclear pore complex plasticity with pan-expansion microscopy. 用泛膨胀显微镜观察核孔复合塑性。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-09-01 Epub Date: 2025-06-12 DOI: 10.1083/jcb.202409120

Kimberly J Morgan, Emma Carley, Alyssa N Coyne, Jeffrey D Rothstein, C Patrick Lusk, Megan C King

{"title":"Visualizing nuclear pore complex plasticity with pan-expansion microscopy.","authors":"Kimberly J Morgan, Emma Carley, Alyssa N Coyne, Jeffrey D Rothstein, C Patrick Lusk, Megan C King","doi":"10.1083/jcb.202409120","DOIUrl":"10.1083/jcb.202409120","url":null,"abstract":"The exploration of cell-type and environmentally responsive nuclear pore complex (NPC) plasticity requires new, accessible tools. Using pan-expansion microscopy (pan-ExM), NPCs were identified by machine learning-facilitated segmentation. They exhibited a large range of diameters with a bias for dilated NPCs at the basal nuclear surface in clusters suggestive of local islands of nuclear envelope tension. Whereas hyperosmotic shock constricted NPCs analogously to those found in annulate lamellae, depletion of LINC complexes specifically eliminated the modest nuclear surface diameter biases. Therefore, LINC complexes may contribute locally to nuclear envelope tension to toggle NPC diameter between dilated, but not constricted, states. Lastly, POM121 shifts from the nuclear ring to the inner ring of the NPC specifically in induced pluripotent stem cell-derived neurons from a patient with C9orf72 amyotrophic lateral sclerosis. Thus, pan-ExM is a powerful tool to visualize NPC plasticity in physiological and pathological contexts at single NPC resolution.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 9","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274960","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

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

The reaction mechanism for glycolysis side product degradation by Parkinson's disease-linked DJ-1. 帕金森病相关DJ-1糖酵解副产物降解的反应机制

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-08-04 Epub Date: 2025-06-04 DOI: 10.1083/jcb.202411078

Aiko Watanabe, Shizuka Ogiwara, Mirei Saito, Masaki Mishima, Masahiro Yamashina, Ryuichiro Ishitani, Yutaka Ito, Keiji Tanaka, Fumika Koyano, Koji Yamano, Hidetaka Kosako, Yoshitaka Moriwaki, Noriyuki Matsuda

{"title":"The reaction mechanism for glycolysis side product degradation by Parkinson's disease-linked DJ-1.","authors":"Aiko Watanabe, Shizuka Ogiwara, Mirei Saito, Masaki Mishima, Masahiro Yamashina, Ryuichiro Ishitani, Yutaka Ito, Keiji Tanaka, Fumika Koyano, Koji Yamano, Hidetaka Kosako, Yoshitaka Moriwaki, Noriyuki Matsuda","doi":"10.1083/jcb.202411078","DOIUrl":"10.1083/jcb.202411078","url":null,"abstract":"DJ-1/PARK7 is the causative gene for hereditary recessive Parkinson's disease. Recent studies have reported that DJ-1 hydrolyzes cyclic 3-phosphoglyceric anhydride (cPGA), a highly reactive metabolite. However, the molecular mechanisms underlying cPGA hydrolase activity have yet to be fully elucidated. To gain a more comprehensive understanding of this activity in DJ-1, we performed molecular simulations that predicted how DJ-1 recognizes and hydrolyzes cPGA. The accuracy of these structural predictions was validated through systematic mutational analyses exemplified by loss of activity with the A107P mutation. Although DJ-1 possesses both cPGA hydrolase and α-oxoaldehyde hydratase activities in vitro, we confirmed that DJ-1 dysfunction caused an increase in cPGA-derived modifications but had no effect on α-oxoaldehyde-derived modifications in cells. Importantly, A107 and P158, pathogenic missense mutation sites found in Parkinson's disease patients, are critical for cPGA hydrolysis both in vitro and in cells. The evidence-based catalytic mechanism for DJ-1 hydrolysis of cPGA that we propose here explains their pathophysiological significance.","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/PMC12135873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215940","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

Taperin bundles F-actin at stereocilia pivot points enabling optimal lifelong mechanosensitivity. 锥形肽束f -肌动蛋白在立体纤毛支点实现最佳终身机械敏感性。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-08-04 Epub Date: 2025-06-05 DOI: 10.1083/jcb.202408026

Inna A Belyantseva, Chang Liu, Abigail K Dragich, Takushi Miyoshi, Sayaka Inagaki, Ayesha Imtiaz, Risa Tona, Karen Sofia Zuluaga-Osorio, Shadan Hadi, Elizabeth Wilson, Eva Morozko, Rafal Olszewski, Rizwan Yousaf, Yuliya Sokolova, Gavin P Riordan, S Andrew Aston, Atteeq U Rehman, Cristina Fenollar Ferrer, Jan Wisniewski, Shoujun Gu, Gowri Nayak, Richard J Goodyear, Jinan Li, Jocelyn F Krey, Talah Wafa, Rabia Faridi, Samuel Mawuli Adadey, Meghan Drummond, Benjamin Perrin, Dennis C Winkler, Matthew F Starost, Hui Cheng, Tracy Fitzgerald, Guy P Richardson, Lijin Dong, Peter G Barr-Gillespie, Michael Hoa, Gregory I Frolenkov, Thomas B Friedman, Bo Zhao

{"title":"Taperin bundles F-actin at stereocilia pivot points enabling optimal lifelong mechanosensitivity.","authors":"Inna A Belyantseva, Chang Liu, Abigail K Dragich, Takushi Miyoshi, Sayaka Inagaki, Ayesha Imtiaz, Risa Tona, Karen Sofia Zuluaga-Osorio, Shadan Hadi, Elizabeth Wilson, Eva Morozko, Rafal Olszewski, Rizwan Yousaf, Yuliya Sokolova, Gavin P Riordan, S Andrew Aston, Atteeq U Rehman, Cristina Fenollar Ferrer, Jan Wisniewski, Shoujun Gu, Gowri Nayak, Richard J Goodyear, Jinan Li, Jocelyn F Krey, Talah Wafa, Rabia Faridi, Samuel Mawuli Adadey, Meghan Drummond, Benjamin Perrin, Dennis C Winkler, Matthew F Starost, Hui Cheng, Tracy Fitzgerald, Guy P Richardson, Lijin Dong, Peter G Barr-Gillespie, Michael Hoa, Gregory I Frolenkov, Thomas B Friedman, Bo Zhao","doi":"10.1083/jcb.202408026","DOIUrl":"10.1083/jcb.202408026","url":null,"abstract":"Stereocilia are rod-like mechanosensory projections consisting of unidirectionally oriented actin filaments that extend into the inner ear hair cell cytoskeleton, forming dense rootlets. Taperin (TPRN) localizes to the narrowed-down base of stereocilia, where they pivot in response to sound and gravity. We show that TPRN-deficient mice have progressive deafness characterized by gradual asynchronous retraction and fusion of outer and inner hair cell stereocilia, followed by synaptic abnormalities. Stereocilia that lack TPRN develop warped rootlets with gradual loss of TRIOBP-5 and ANKRD24 from mechanosensory rows starting postnatally. In contrast, TPRN overexpression causes excessive F-actin bundling, extra rows, and over-elongation of stereocilia during development. Purified full-length mouse TPRN cross-links F-actin into bendable bundles reflecting in vivo data. This F-actin-bundling ability is attributed to the TPRN N-terminal region. TPRN interacts with the membrane receptor PTPRQ, connecting the F-actin core to the plasma membrane, stabilizing stereocilia. Thus, TPRN is a specialized F-actin bundler strategically located to augment stereocilia rootlet formation and their pivot point flexibility for sustained sound-induced deflections.","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/PMC12139522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225562","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

Metabolic adaptations of micrometastases alter EV production to generate invasive microenvironments. 微转移的代谢适应改变了EV的产生，从而产生侵入性微环境。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-08-04 Epub Date: 2025-06-09 DOI: 10.1083/jcb.202405061

Michalis Gounis, America V Campos, Engy Shokry, Louise Mitchell, Ruhi Deshmukh, Emmanuel Dornier, Nicholas Rooney, Sandeep Dhayade, Luis Pardo, Madeleine Moore, David Novo, Jenna Mowat, Craig Jamieson, Emily Kay, Sara Zanivan, Nikki R Paul, Claire Mitchell, Colin Nixon, Iain Macpherson, Saverio Tardito, David Sumpton, Karen Blyth, Jim C Norman, Cassie J Clarke

{"title":"Metabolic adaptations of micrometastases alter EV production to generate invasive microenvironments.","authors":"Michalis Gounis, America V Campos, Engy Shokry, Louise Mitchell, Ruhi Deshmukh, Emmanuel Dornier, Nicholas Rooney, Sandeep Dhayade, Luis Pardo, Madeleine Moore, David Novo, Jenna Mowat, Craig Jamieson, Emily Kay, Sara Zanivan, Nikki R Paul, Claire Mitchell, Colin Nixon, Iain Macpherson, Saverio Tardito, David Sumpton, Karen Blyth, Jim C Norman, Cassie J Clarke","doi":"10.1083/jcb.202405061","DOIUrl":"10.1083/jcb.202405061","url":null,"abstract":"Altered cellular metabolism has been associated with the acquisition of invasive phenotypes during metastasis. To study this, we combined a genetically engineered mouse model of mammary carcinoma with syngeneic transplantation and primary tumor resection to generate isogenic cells from primary tumors and their corresponding lung micrometastases. Metabolic analyses indicated that micrometastatic cells increase proline production at the expense of glutathione synthesis, leading to a reduction in total glutathione levels. Micrometastatic cells also have altered sphingomyelin metabolism, leading to increased intracellular levels of specific ceramides. The combination of these metabolic adaptations alters extracellular vesicle (EV) production to render the microenvironment more permissive for invasion. Indeed, micrometastatic cells shut down Rab27-dependent production of EVs and, instead, switch on neutral sphingomyelinase-2 (nSM2)-dependent EV release. EVs released in an nSM2-dependent manner from micrometastatic cells, in turn, influence the ability of fibroblasts to deposit extracellular matrix, which promotes cancer cell invasiveness. These data provide evidence that metabolic rewiring drives invasive processes in metastasis by influencing EV release.","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/PMC12147664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248074","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

CNTD1 is crucial for crossover formation in female meiosis and for establishing the ovarian reserve. CNTD1在女性减数分裂的交叉形成和卵巢储备的建立中起着至关重要的作用。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-08-04 Epub Date: 2025-06-09 DOI: 10.1083/jcb.202401021

Anna J Wood, Rania M Ahmed, Leah E Simon, Rachel A Bradley, Stephen Gray, Ian D Wolff, Paula E Cohen

{"title":"CNTD1 is crucial for crossover formation in female meiosis and for establishing the ovarian reserve.","authors":"Anna J Wood, Rania M Ahmed, Leah E Simon, Rachel A Bradley, Stephen Gray, Ian D Wolff, Paula E Cohen","doi":"10.1083/jcb.202401021","DOIUrl":"10.1083/jcb.202401021","url":null,"abstract":"In meiotic prophase I, hundreds of DNA double-strand breaks are formed and subsequently repaired as noncrossovers or crossovers (COs). COs are essential for accurate chromosome segregation during the first meiotic division, and errors in this process result in aneuploidy, birth defects, or infertility. Such errors are more pronounced in females compared with males, indicating that CO regulation and surveillance are sexually dimorphic. We demonstrate here dual roles of cyclin N-terminal domain containing 1 (CNTD1) in ensuring appropriate CO between homologous chromosomes in oocytes and in establishing the pool of follicles in the postnatal ovary. CNTD1-deficient oocytes fail to form COs and exhibit a severely depleted follicle pool shortly after birth, which is temporally distinct from previously reported CO mutants. Further investigation indicates that follicle loss is CHK2-dependent, resulting from inappropriate retention of HORMAD1 and the absence of SKP1. These findings indicate that CNTD1 plays novel roles in CO designation and establishment of the follicular reserve in female mammals.","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/PMC12147665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248073","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

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