Journal of Cell Biology最新文献_第10页

Acidosis attenuates the hypoxic stabilization of HIF-1α by activating lysosomal degradation. 酸中毒通过激活溶酶体降解来减弱HIF-1α的缺氧稳定性。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2025-06-24 DOI: 10.1083/jcb.202409103

Bobby White,Zhenyi Wang,Matthew Dean,Johanna Michl,Natalia Nieora,Sarah Flannery,Iolanda Vendrell,Roman Fischer,Alzbeta Hulikova,Pawel Swietach

{"title":"Acidosis attenuates the hypoxic stabilization of HIF-1α by activating lysosomal degradation.","authors":"Bobby White,Zhenyi Wang,Matthew Dean,Johanna Michl,Natalia Nieora,Sarah Flannery,Iolanda Vendrell,Roman Fischer,Alzbeta Hulikova,Pawel Swietach","doi":"10.1083/jcb.202409103","DOIUrl":"https://doi.org/10.1083/jcb.202409103","url":null,"abstract":"Hypoxia-inducible factors (HIFs) mediate cellular responses to low oxygen, notably enhanced fermentation that acidifies poorly perfused tissues and may eventually become more damaging than adaptive. How pH feeds back on hypoxic signaling is unclear but critical to investigate because acidosis and hypoxia are mechanistically coupled in diffusion-limited settings, such as tumors. Here, we examined the pH sensitivity of hypoxic signaling in colorectal cancer cells that can survive acidosis. HIF-1α stabilization under acidotic hypoxia was transient, declining over 48 h. Proteomic analyses identified responses that followed HIF-1α, including canonical HIF targets (e.g., CA9, PDK1), but these did not reflect a proteome-wide downregulation. Enrichment analyses suggested a role for lysosomal degradation. Indeed, HIF-1α destabilization was blocked by inactivating lysosomes, but not proteasome inhibitors. Acidotic hypoxia stimulated lysosomal activity and autophagy via mammalian target of rapamycin complex I (mTORC1), resulting in HIF-1α degradation. This response protects cells from excessive acidification by unchecked fermentation. Thus, alkaline conditions are permissive for at least some aspects of HIF-1α signaling.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"19 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370325","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

Cellular wound healing: A two-step mechanism of plasma membrane repair by annexins and calpains. 细胞伤口愈合：膜联蛋白和钙蛋白的两步质膜修复机制。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2025-06-18 DOI: 10.1083/jcb.202505027

Sabina Elmi,Jesper Nylandsted

引用次数: 0

The primary cilium as a gatekeeper of FGFR2 function. 初级纤毛作为FGFR2功能的守门人。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2025-06-12 DOI: 10.1083/jcb.202505022

Raman Kaushik,Raj K Ladher

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 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

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 6.4 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":6.4,"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

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