Journal of cell science最新文献_第2页

Phosphorylation-induced SUMOylation promotes Ulk4 condensation at ciliary tip to transduce Hedgehog signal.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-04-02 DOI: 10.1242/jcs.263695

Mengmeng Zhou, Yuhong Han, Jin Jiang

{"title":"Phosphorylation-induced SUMOylation promotes Ulk4 condensation at ciliary tip to transduce Hedgehog signal.","authors":"Mengmeng Zhou, Yuhong Han, Jin Jiang","doi":"10.1242/jcs.263695","DOIUrl":"https://doi.org/10.1242/jcs.263695","url":null,"abstract":"Hedgehog (Hh) signaling controls embryonic development and adult tissue homeostasis through the Gli family of transcription factors. In vertebrates, Hh signal transduction depends on the primary cilium where Gli is thought to be activated at the ciliary tip, but the underlying mechanism has remained poorly understood. Here we provide evidence that two Unc-51-like kinase (Ulk) family members Stk36 and Ulk4 regulate Gli2 ciliary tip localization and activation through phosphorylation and SUMOylation-mediated condensation in response to Shh. We find that Stk36-mediated phosphorylation of Ulk4 promotes its SUMOylation in response to Shh, and the subsequent interaction between SUMO and a SUMO-Interacting-Motif (SIM) in the C-terminal region of Ulk4 drives Ulk4 self-assembly to form biomolecular condensates that also recruit Stk36 and Gli2. SUMOylation or SIM-deficient Ulk4 failed to accumulate at ciliary tip to activate Gli2 whereas phospho-mimetic mutation of Ulk4 sufficed to drive Ulk4/Stk36/Gli2 condensation at ciliary tip, leading to constitutive Shh pathway activation in a manner dependent on Ulk4 SUMOylation. Taken together, our results suggest that phosphorylation-dependent SUMOylation of Ulk4 promotes kinase-substrate condensation at ciliary tip to transduce the Hh signal.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

ATG9A vesicles are a subtype of intracellular nanovesicle.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-04-01 Epub Date: 2025-04-09 DOI: 10.1242/jcs.263852

Mary Fesenko, Daniel J Moore, Peyton Ewbank, Elizabeth Courthold, Stephen J Royle

引用次数: 0

Announcing the JCS-David Stephens Prize and the 2024 winner Anja Konietzny. 宣布JCS-David Stephens奖和2024年获奖者Anja Konietzny。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-04-01 Epub Date: 2025-04-04 DOI: 10.1242/jcs.263973

Michael Way

引用次数: 0

Regulation of cell migration by extracellular matrix mechanics at a glance.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-04-01 Epub Date: 2025-04-04 DOI: 10.1242/jcs.263574

Cole Allan, Ovijit Chaudhuri

引用次数: 0

Remembering David Stephens (1971-2024). 缅怀戴维-斯蒂芬斯（1971-2024）。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-04-01 Epub Date: 2025-04-04 DOI: 10.1242/jcs.263972

Jon Lane, George Banting

引用次数: 0

Practical considerations for data exploration in quantitative cell biology.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-04-01 Epub Date: 2025-04-07 DOI: 10.1242/jcs.263801

Joanna W Pylvänäinen, Hanna Grobe, Guillaume Jacquemet

引用次数: 0

Vps41 functions as a molecular ruler for HOPS tethering complex function.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-03-31 DOI: 10.1242/jcs.263788

Caroline König, Dmitry Shvarev, Jieqiong Gao, Eduard Haar, Nicole Susan, Kathrin Auffarth, Lars Langemeyer, Arne Moeller, Christian Ungermann

{"title":"Vps41 functions as a molecular ruler for HOPS tethering complex function.","authors":"Caroline König, Dmitry Shvarev, Jieqiong Gao, Eduard Haar, Nicole Susan, Kathrin Auffarth, Lars Langemeyer, Arne Moeller, Christian Ungermann","doi":"10.1242/jcs.263788","DOIUrl":"https://doi.org/10.1242/jcs.263788","url":null,"abstract":"Fusion at the lysosome (or the yeast vacuole) requires the conserved hexameric HOPS tethering complex. HOPS binds to the vacuolar Rab7-like GTPase Ypt7 via its subunits Vps41 and Vps39 and supports fusion by promoting SNARE assembly. In contrast to its sister complex CORVET, the Ypt7-interacting domain of Vps41 in the HOPS complex is connected to the core by a long, extended α-solenoid domain. Here, we show that this solenoid acts as a molecular ruler to position the Ypt7-interaction part of Vps41 relative to the core of HOPS to support function. Mutant complexes with a shortened or extended α-solenoid part in Vps41 still tether membranes, but fail to efficiently support their fusion. In vivo, Vps41 mutants grow poorly, show defects in vacuolar morphology, endolysosomal sorting and autophagy. Importantly, if a length-compensating linker is inserted instead of the shortened α-solenoid, these defects are rescued. This suggests that the Rab-specific Vps41 subunit requires the exact length, but not the α-solenoid domain for functionality, implying a revised model how HOPS supports fusion.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Phosphorylation of the Aly3 C-terminus impedes aberrant endocytosis of Schizosaccharomyces pombe hexose transporter Ght5.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-03-31 DOI: 10.1242/jcs.263572

Yusuke Toyoda, Fumie Masuda, Shigeaki Saitoh

{"title":"Phosphorylation of the Aly3 C-terminus impedes aberrant endocytosis of Schizosaccharomyces pombe hexose transporter Ght5.","authors":"Yusuke Toyoda, Fumie Masuda, Shigeaki Saitoh","doi":"10.1242/jcs.263572","DOIUrl":"https://doi.org/10.1242/jcs.263572","url":null,"abstract":"In fission yeast, Schizosaccharomyces pombe, transcriptional upregulation and cell-surface localization of the hexose transporter, Ght5, are required for cell proliferation in low glucose. As the target of rapamycin complex 2 (TORC2) signaling pathway inhibits α-arrestin Aly3-dependent endocytosis of Ght5, we hypothesized that phosphorylation inhibits this endocytosis. To identify phosphorylation sites required for proliferation in low glucose, putatively phosphorylated serine/threonine residues of Aly3 and Ght5 were replaced with alanine. C-terminal serine residues of Aly3, but not Ght5, were necessary for proliferation in low glucose. Expression of Aly3 unphosphorylated at the C-terminus led to increased ubiquitination and vacuolar accumulation of Ght5 in low glucose, but reversion of one of the alanine residues to serine reversed those defects. Also, Aly3 physically interacted with the HECT-type ubiquitin ligases, Pub1 and Pub3, and these interactions were required for surface localization of Ght5 and proliferation in low glucose. This study reveals mechanisms by which Aly3 is regulated so that fission yeast can adapt to nutritional stress.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Select autosomal dominant DFNA11 deafness mutations activate Myo7A targeting in epithelial cells.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-03-20 DOI: 10.1242/jcs.263982

Prashun Acharya, Garima Thapa, Xiayi Liao, Samaneh Matoo, Maura J Graves, Sarah Y Atallah, Ashna K Tipirneni, Tram Nguyen, Niki M Chhabra, Jaden Maschack, Mackenzie R Herod, Favour A Ohaezu, Alder Robison, Ashwini Mudaliyar, Jasvinder Bharaj, Nicole Roeser, Katherine Holmes, Vishwaas Nayak, Rayah Alsayed, Benjamin J Perrin, Scott W Crawley

{"title":"Select autosomal dominant DFNA11 deafness mutations activate Myo7A targeting in epithelial cells.","authors":"Prashun Acharya, Garima Thapa, Xiayi Liao, Samaneh Matoo, Maura J Graves, Sarah Y Atallah, Ashna K Tipirneni, Tram Nguyen, Niki M Chhabra, Jaden Maschack, Mackenzie R Herod, Favour A Ohaezu, Alder Robison, Ashwini Mudaliyar, Jasvinder Bharaj, Nicole Roeser, Katherine Holmes, Vishwaas Nayak, Rayah Alsayed, Benjamin J Perrin, Scott W Crawley","doi":"10.1242/jcs.263982","DOIUrl":"10.1242/jcs.263982","url":null,"abstract":"Myosin-7A (Myo7A) is a motor protein crucial for the organization and function of stereocilia, specialized actin-rich protrusions on the surface of inner ear hair cells that mediate hearing. Mutations in Myo7A cause several forms of genetic hearing loss, including autosomal dominant DFNA11 deafness. Despite its importance, the structural elements that control Myo7A within cells are not well understood. In this study, we used cultured kidney epithelial cells to screen for mutations that activate the motor-dependent targeting of Myo7A to the tips of apical microvilli on these cells. Our findings reveal that Myo7A targeting is regulated by specific IQ motifs within its lever arm, and that this regulation can function at least partially independent of its tail sequence. Importantly, we demonstrate that many of the DFNA11 deafness mutations reported in patients activate Myo7A targeting, providing a potential explanation for the autosomal dominant genetics of this form of deafness.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Rab40 GTPases regulate AMBRA1-mediated transcription and cell migration.

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-03-20 DOI: 10.1242/jcs.263707

Revathi Sampath, Katherine Vaeth, Valeryia Mikalayeva, Vytenis Arvydas Skeberdis, Rytis Prekeris, Ke-Jun Han

{"title":"Rab40 GTPases regulate AMBRA1-mediated transcription and cell migration.","authors":"Revathi Sampath, Katherine Vaeth, Valeryia Mikalayeva, Vytenis Arvydas Skeberdis, Rytis Prekeris, Ke-Jun Han","doi":"10.1242/jcs.263707","DOIUrl":"10.1242/jcs.263707","url":null,"abstract":"The Rab40 subfamily are unique small monomeric GTPases that form CRL5-based ubiquitin E3 ligase complex and regulate ubiquitylation of specific target proteins. Recent studies have shown that Rab40s play an important role in regulating cell migration, but the underlying mechanisms of Rab40/CRL5 complex function are still not fully understood. In this study we identified AMBRA1 as a novel binding partner of Rab40 GTPases and showed that this interaction mediates a bi-directional crosstalk between CRL4 and CRL5 E3 ligases. Importantly, we found that Rab40/CRL5 ubiquitylates AMBRA1, which does not result in AMBRA1 degradation, but instead it seems to induce AMBRA1-dependent regulation of gene transcription. The global transcriptional profiles identified by RNA-seq showed that AMBRA1 regulates transcription of genes related to cell adhesion and migration. Additionally, we have shown that AMBRA1-dependent transcription regulation does not require the enzymatic activity of AMBRA1/CRL4, and that Rab40-induced AMBRA1 ubiquitylation leads to dissociation of AMBRA1/CRL4 complex. Taken together, our findings reveal a novel function of Rab40/CRL5 complex as an important regulator for AMBRA1-dependent transcription of genes involved in cell migration.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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