Journal of Cell Biology最新文献_第2页

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

Plasticity of mitotic cyclins in promoting the G2-M transition. 有丝分裂周期蛋白在促进G2-M转变中的可塑性。

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.202409219

Adrijana Crncec, Ho Wai Lau, Lau Yan Ng, Hoi Tang Ma, Joyce P Y Mak, Hon Fung Choi, Tsz Kwan Yeung, Randy Yat Choi Poon

{"title":"Plasticity of mitotic cyclins in promoting the G2-M transition.","authors":"Adrijana Crncec, Ho Wai Lau, Lau Yan Ng, Hoi Tang Ma, Joyce P Y Mak, Hon Fung Choi, Tsz Kwan Yeung, Randy Yat Choi Poon","doi":"10.1083/jcb.202409219","DOIUrl":"10.1083/jcb.202409219","url":null,"abstract":"Cyclins and cyclin-dependent kinases (CDKs) orchestrate key events in the cell cycle. However, the uniqueness of individual mitotic cyclins has been a long-standing puzzle. By rapidly removing cyclins in G2 human cells, we found that deficiency of B-type cyclins attenuates mitotic onset and uncouples the G2-M kinase network from mitosis, resulting in sustained activation of PLK1 and cyclin A-CDK1. This culminates in mitotic slippage without completing nuclear envelope breakdown. Remarkably, elevating cyclin A several-fold above its endogenous level is adequate to restore mitosis, allowing cells to survive without B-type cyclins. In contrast, cyclin A is rate-limiting but not essential for G2-M due to compensation by endogenous cyclin B1-CDK2, a non-canonical pair. These findings challenge the traditional indispensable roles of different cyclins and highlight their plasticity. Due to the high malleability of the A- and B-type cyclins, cancer cells may be able to place different weights on different cyclins, while maintaining sufficient CDK activities for successful mitosis.","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/PMC11980681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811431","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

ESCRT-I and PTPN23 mediate microautophagy of ubiquitylated tau aggregates. ESCRT-I和PTPN23介导泛素化tau聚集体的微自噬。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-06-02 Epub Date: 2025-04-08 DOI: 10.1083/jcb.202406120

Yusen Men, Shoshiro Hirayama, Shinpei Ao, Yasuyuki Sakurai, Yuri Shibata, Megan Lo, Yusuke Sato, Shigeo Murata

引用次数: 0

Extracellular vesicles adhere to cells primarily by interactions of integrins and GM1 with laminin. 细胞外囊泡粘附细胞主要是通过整合素和GM1与层粘连蛋白的相互作用。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-06-02 Epub Date: 2025-04-30 DOI: 10.1083/jcb.202404064

Tatsuki Isogai, Koichiro M Hirosawa, Miki Kanno, Ayano Sho, Rinshi S Kasai, Naoko Komura, Hiromune Ando, Keiko Furukawa, Yuhsuke Ohmi, Koichi Furukawa, Yasunari Yokota, Kenichi G N Suzuki

{"title":"Extracellular vesicles adhere to cells primarily by interactions of integrins and GM1 with laminin.","authors":"Tatsuki Isogai, Koichiro M Hirosawa, Miki Kanno, Ayano Sho, Rinshi S Kasai, Naoko Komura, Hiromune Ando, Keiko Furukawa, Yuhsuke Ohmi, Koichi Furukawa, Yasunari Yokota, Kenichi G N Suzuki","doi":"10.1083/jcb.202404064","DOIUrl":"https://doi.org/10.1083/jcb.202404064","url":null,"abstract":"Tumor-derived extracellular vesicles (EVs) have attracted significant attention, yet the molecular mechanisms that govern their specific binding to recipient cells remain elusive. Our in vitro study utilizing single-particle tracking demonstrated that integrin heterodimers comprising α6β4 and α6β1 and ganglioside, GM1, are responsible for the binding of small EV (sEV) subtypes to laminin. EVs derived from four distinct tumor cell lines, regardless of size, exhibited high binding affinities for laminin but not for fibronectin, although fibronectin receptors are abundant in EVs and have functional roles in EV-secreting cells. Our findings revealed that integrins in EVs bind to laminin via the conventional molecular interface, facilitated by CD151 rather than by inside-out signaling of talin-1 and kindlin-2. Super-resolution movie observation revealed that sEV integrins bind only to laminin on living recipient cells. Furthermore, sEVs bound to HUVEC and induced cell branching morphogenesis in a laminin-dependent manner. Thus, we demonstrated that EVs predominantly bind to laminin on recipient cells, which is indispensable for cell responses.","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/PMC12042775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001816","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

CCSer2 gates dynein activity at the cell periphery. CCSer2在细胞外围调控动力蛋白的活性。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-06-02 Epub Date: 2025-04-22 DOI: 10.1083/jcb.202406153

Juliana L Zang, Daytan Gibson, Ann-Marie Zheng, Wanjing Shi, John P Gillies, Chris Stein, Catherine M Drerup, Morgan E DeSantis

{"title":"CCSer2 gates dynein activity at the cell periphery.","authors":"Juliana L Zang, Daytan Gibson, Ann-Marie Zheng, Wanjing Shi, John P Gillies, Chris Stein, Catherine M Drerup, Morgan E DeSantis","doi":"10.1083/jcb.202406153","DOIUrl":"https://doi.org/10.1083/jcb.202406153","url":null,"abstract":"Cytoplasmic dynein-1 (dynein) is a microtubule-associated, minus end-directed motor that traffics hundreds of different cargos. Dynein must discriminate between cargos and traffic them at the appropriate time from the correct cellular region. How dynein's trafficking activity is regulated in time or cellular space remains poorly understood. Here, we identify CCSer2 as the first known protein to gate dynein activity in the spatial dimension. CCSer2 promotes the migration of developing zebrafish primordium cells, macrophages, and cultured human cells by facilitating the trafficking of cargos that are acted on by peripherally localized dynein. Our data suggest that CCSer2 disfavors the interaction between dynein and its regulator Ndel1 at the cell edge, resulting in localized dynein activation. These findings support a model where the spatial specificity of dynein is achieved by the localization of proteins that trigger Ndel1's release from dynein. We propose that CCSer2 defines a broader class of proteins that activate dynein in distinct microenvironments via regulating Ndel1-dynein interaction.","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/PMC12013514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010944","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

An advanced toolset to manipulate and monitor subcellular phosphatidylinositol 3,5-bisphosphate. 先进的工具集操作和监测亚细胞磷脂酰肌醇3,5-二磷酸。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-06-02 Epub Date: 2025-03-26 DOI: 10.1083/jcb.202408158

Joshua G Pemberton, Isobel Barlow-Busch, Meredith L Jenkins, Matthew A H Parson, Farkas Sarnyai, Seyma Nur Bektas, Yeun Ju Kim, John E Heuser, John E Burke, Tamas Balla

{"title":"An advanced toolset to manipulate and monitor subcellular phosphatidylinositol 3,5-bisphosphate.","authors":"Joshua G Pemberton, Isobel Barlow-Busch, Meredith L Jenkins, Matthew A H Parson, Farkas Sarnyai, Seyma Nur Bektas, Yeun Ju Kim, John E Heuser, John E Burke, Tamas Balla","doi":"10.1083/jcb.202408158","DOIUrl":"10.1083/jcb.202408158","url":null,"abstract":"Phosphatidylinositol (PI) 3,5-bisphosphate (PI(3,5)P2) is a minor inositol-containing phospholipid that serves as an important regulator of endolysosomal functions. However, the precise sites of subcellular enrichment and molecular targets of this regulatory lipid are poorly understood. Here, we describe the generation and detailed characterization of a short engineered catalytic fragment of the human PIKfyve enzyme, which potently converts PI 3-phosphate to PI(3,5)P2. This novel tool allowed for the evaluation of reported PI(3,5)P2-sensitive biosensors and showed that the recently identified phox homology (PX) domain of the Dictyostelium discoideum (Dd) protein, SNXA, can be used to monitor the production of PI(3,5)P2 in live cells. Modification and adaptation of the DdSNXAPX-based probes into compartment-specific bioluminescence resonance energy transfer-based biosensors allows for the real-time monitoring of PI(3,5)P2 generation within the endocytic compartments of entire cell populations. Collectively, these molecular tools should allow for exciting new studies to better understand the cellular processes controlled by localized PI(3,5)P2 metabolism.","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/PMC11940380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730234","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

Structural characterization and inhibition of the interaction between ch-TOG and TACC3. ch-TOG与TACC3相互作用的结构表征及抑制作用。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-06-02 Epub Date: 2025-03-19 DOI: 10.1083/jcb.202407002

James Shelford, Selena G Burgess, Elena Rostkova, Mark W Richards, Gabrielle Larocque, Josephina Sampson, Christian Tiede, Alistair J Fielding, Tina Daviter, Darren C Tomlinson, Antonio N Calabrese, Mark Pfuhl, Richard Bayliss, Stephen J Royle

{"title":"Structural characterization and inhibition of the interaction between ch-TOG and TACC3.","authors":"James Shelford, Selena G Burgess, Elena Rostkova, Mark W Richards, Gabrielle Larocque, Josephina Sampson, Christian Tiede, Alistair J Fielding, Tina Daviter, Darren C Tomlinson, Antonio N Calabrese, Mark Pfuhl, Richard Bayliss, Stephen J Royle","doi":"10.1083/jcb.202407002","DOIUrl":"10.1083/jcb.202407002","url":null,"abstract":"The mitotic spindle is a bipolar array of microtubules, radiating from the poles which each contain a centrosome, embedded in pericentriolar material. Two proteins, ch-TOG and TACC3, have multiple functions at the mitotic spindle due to operating either alone, together, or in complex with other proteins. To distinguish these activities, we need new molecular tools to dissect their function. Here, we present the structure of the α-helical bundle domain of ch-TOG that mediates its interaction with TACC3 and a structural model describing the interaction, supported by biophysical and biochemical data. We have isolated Affimer tools to precisely target the ch-TOG-binding site on TACC3 in live cells, which displace ch-TOG without affecting the spindle localization of other protein complex components. Inhibition of the TACC3-ch-TOG interaction led unexpectedly to fragmentation of the pericentriolar material in metaphase cells and delayed mitotic progression, uncovering a novel role of TACC3-ch-TOG in maintaining pericentriolar material integrity during mitosis to ensure timely cell division.","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/PMC11921806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656930","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

Importin-9 and a TPR domain protein MpH drive periodic patterning of ciliary arrays in Tetrahymena. 进口蛋白9和TPR结构域蛋白MpH驱动四膜虫纤毛阵列的周期性模式。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-06-02 Epub Date: 2025-03-28 DOI: 10.1083/jcb.202409057

Anushi Suwaneththiya Deraniyagala, Wolfgang Maier, Mireya Parra, Elise Nanista, Deborah Oluwabukola Sowunmi, Michael Hassan, Nathan Chasen, Sunita Sharma, Karl F Lechtreck, Eric S Cole, Natalia Bernardes, Yuh Min Chook, Jacek Gaertig

{"title":"Importin-9 and a TPR domain protein MpH drive periodic patterning of ciliary arrays in Tetrahymena.","authors":"Anushi Suwaneththiya Deraniyagala, Wolfgang Maier, Mireya Parra, Elise Nanista, Deborah Oluwabukola Sowunmi, Michael Hassan, Nathan Chasen, Sunita Sharma, Karl F Lechtreck, Eric S Cole, Natalia Bernardes, Yuh Min Chook, Jacek Gaertig","doi":"10.1083/jcb.202409057","DOIUrl":"10.1083/jcb.202409057","url":null,"abstract":"We explored how the number of structures is determined in an intracellular organelle series. In Tetrahymena, the oral apparatus contains three diagonal ciliary rows: M1, M2, and M3. During development, the M rows emerge by sequential segmentation of a group of basal bodies, starting with the longest and most anterior M1 and ending with the shortest and most posterior M3. The mpD-1 and mpH-1 alleles increase and decrease the number of M rows, respectively. We identify MpH as a TPR protein and MpD as an importin-9. Both proteins localize to the M rows and form concentration gradients. MpH is a row elongation factor whose loss shortens all M rows and often prevents the formation of M3. MpD limits row initiation after the emergence of M2. MpD could be a part of a negative feedback loop that limits row initiation when M1 assembly is properly advanced. We conclude that the forming oral apparatus has properties of a semi-autonomous intracellular developmental field.","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/PMC11951933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730249","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

Sorting nexin 10 regulates lysosomal ionic homeostasis via ClC-7 by controlling PI(3,5)P2. 分选连接蛋白10通过控制PI(3,5)P2通过ClC-7调控溶酶体离子稳态。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-06-02 Epub Date: 2025-03-26 DOI: 10.1083/jcb.202408174

Jing Ze Wu, Joshua G Pemberton, Shin Morioka, Junko Sasaki, Priya Bablani, Takehiko Sasaki, Tamas Balla, Sergio Grinstein, Spencer A Freeman

{"title":"Sorting nexin 10 regulates lysosomal ionic homeostasis via ClC-7 by controlling PI(3,5)P2.","authors":"Jing Ze Wu, Joshua G Pemberton, Shin Morioka, Junko Sasaki, Priya Bablani, Takehiko Sasaki, Tamas Balla, Sergio Grinstein, Spencer A Freeman","doi":"10.1083/jcb.202408174","DOIUrl":"10.1083/jcb.202408174","url":null,"abstract":"Mutations or ablation of Snx10 are associated with neurodegeneration, blindness, and osteopetrosis. The similarities between osteoclasts and macrophages prompted us to analyze the role of Snx10 in phagocytosis. Deletion of Snx10 impaired phagosome resolution. Defective resolution was caused by reduced Cl- accumulation within (phago)lysosomes, replicating the phenotype reported in macrophages lacking ClC-7, a lysosomal 2Cl-/H+ antiporter. Delivery of ClC-7 to (phago)lysosomes was unaffected by ablation of Snx10, but its activity was markedly depressed. Snx10 was found to regulate ClC-7 activity indirectly by controlling the availability of phosphatidylinositol 3,5-bisphosphate (PI[3,5]P2), which inhibits ClC-7. By limiting the formation of PI(3,5)P2, Snx10 enables the accumulation of luminal Cl- in phagosomes and lysosomes, which is required for their optimal degradative function. Our data suggest that Snx10 regulates the delivery of PI 3-phosphate (PI[3]P), the precursor of PI(3,5)P2, from earlier endocytic compartments to (phago)lysosomes. By controlling the traffic of phosphoinositides, Snx10 regulates phagosomal resolution and possibly accounts for the impaired bone resorption in Snx10-deficient osteoclasts.","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/PMC11940377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730257","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

Correction: PINK1 controls RTN3L-mediated ER autophagy by regulating peripheral tubule junctions. 纠正：PINK1通过调节外周小管连接来控制rtn3l介导的内质网自噬。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-06-02 Epub Date: 2025-05-19 DOI: 10.1083/jcb.20240719305082025c

Ravi Chidambaram, Kamal Kumar, Smriti Parashar, Gowsalya Ramachandran, Shuliang Chen, Susan Ferro-Novick

引用次数: 0