Journal of Cell Biology最新文献_第4页

Tip60-mediated Rheb acetylation links palmitic acid with mTORC1 activation and insulin resistance. Tip60 介导的 Rheb 乙酰化将棕榈酸与 mTORC1 激活和胰岛素抵抗联系起来。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-12-02 Epub Date: 2024-10-18 DOI: 10.1083/jcb.202309090

Zengqi Zhao, Qiang Chen, Xiaojun Xiang, Weiwei Dai, Wei Fang, Kun Cui, Baolin Li, Qiangde Liu, Yongtao Liu, Yanan Shen, Yueru Li, Wei Xu, Kangsen Mai, Qinghui Ai

{"title":"Tip60-mediated Rheb acetylation links palmitic acid with mTORC1 activation and insulin resistance.","authors":"Zengqi Zhao, Qiang Chen, Xiaojun Xiang, Weiwei Dai, Wei Fang, Kun Cui, Baolin Li, Qiangde Liu, Yongtao Liu, Yanan Shen, Yueru Li, Wei Xu, Kangsen Mai, Qinghui Ai","doi":"10.1083/jcb.202309090","DOIUrl":"10.1083/jcb.202309090","url":null,"abstract":"Excess dietary intake of saturated fatty acids (SFAs) induces glucose intolerance and metabolic disorders. In contrast, unsaturated fatty acids (UFAs) elicit beneficial effects on insulin sensitivity. However, it remains elusive how SFAs and UFAs signal differentially toward insulin signaling to influence glucose homeostasis. Here, using a croaker model, we report that dietary palmitic acid (PA), but not oleic acid or linoleic acid, leads to dysregulation of mTORC1, which provokes systemic insulin resistance. Mechanistically, we show that PA profoundly elevates acetyl-CoA derived from mitochondrial fatty acid β oxidation to intensify Tip60-mediated Rheb acetylation, which triggers mTORC1 activation by promoting the interaction between Rheb and FKBPs. Subsequently, hyperactivation of mTORC1 enhances IRS1 serine phosphorylation and inhibits TFEB-mediated IRS1 transcription, inducing impairment of insulin signaling. Collectively, our results reveal a conserved molecular insight into the mechanism by which Tip60-mediated Rheb acetylation induces mTORC1 activation and insulin resistance under the PA condition, which may provide therapeutic avenues to intervene in the development of T2D.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 12","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11489267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466350","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

Organization of a cytoskeletal superstructure in the apical domain of intestinal tuft cells. 肠绒毛细胞顶端结构中的细胞骨架上层结构组织

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-12-02 Epub Date: 2024-10-01 DOI: 10.1083/jcb.202404070

Jennifer B Silverman, Evan E Krystofiak, Leah R Caplan, Ken S Lau, Matthew J Tyska

{"title":"Organization of a cytoskeletal superstructure in the apical domain of intestinal tuft cells.","authors":"Jennifer B Silverman, Evan E Krystofiak, Leah R Caplan, Ken S Lau, Matthew J Tyska","doi":"10.1083/jcb.202404070","DOIUrl":"10.1083/jcb.202404070","url":null,"abstract":"Tuft cells are a rare epithelial cell type that play important roles in sensing and responding to luminal antigens. A defining morphological feature of this lineage is the actin-rich apical \"tuft,\" which contains large fingerlike protrusions. However, details of the cytoskeletal ultrastructure underpinning the tuft, the molecules involved in building this structure, or how it supports tuft cell biology remain unclear. In the context of the small intestine, we found that tuft cell protrusions are supported by long-core bundles that consist of F-actin crosslinked in a parallel and polarized configuration; they also contain a tuft cell-specific complement of actin-binding proteins that exhibit regionalized localization along the bundle axis. Remarkably, in the sub-apical cytoplasm, the array of core actin bundles interdigitates and co-aligns with a highly ordered network of microtubules. The resulting cytoskeletal superstructure is well positioned to support subcellular transport and, in turn, the dynamic sensing functions of the tuft cell that are critical for intestinal homeostasis.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 12","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347299","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

Fine-tuning stress responses by auxiliary feedback loops that sense damage repair. 通过感知损伤修复的辅助反馈回路微调应激反应

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-12-02 Epub Date: 2024-11-15 DOI: 10.1083/jcb.202410205

Axel Mogk, Fabian den Brave

引用次数: 0

Migratory autolysosome disposal mitigates lysosome damage. 迁移性自溶体处理减轻了溶酶体损伤。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-12-02 Epub Date: 2024-09-30 DOI: 10.1083/jcb.202403195

Takami Sho, Ying Li, Haifeng Jiao, Li Yu

引用次数: 0

Preserve or destroy: Orphan protein proteostasis and the heat shock response. 保存还是毁灭孤儿蛋白蛋白稳态与热休克反应

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-12-02 Epub Date: 2024-11-15 DOI: 10.1083/jcb.202407123

Asif Ali, Sarah Paracha, David Pincus

引用次数: 0

Mitochondrial-derived compartments are multilamellar domains that encase membrane cargo and cytosol. 线粒体源性区室是一个多纤层结构域，可容纳膜货物和细胞膜。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-11-04 Epub Date: 2024-08-13 DOI: 10.1083/jcb.202307035

Zachary N Wilson, Matt West, Alyssa M English, Greg Odorizzi, Adam L Hughes

{"title":"Mitochondrial-derived compartments are multilamellar domains that encase membrane cargo and cytosol.","authors":"Zachary N Wilson, Matt West, Alyssa M English, Greg Odorizzi, Adam L Hughes","doi":"10.1083/jcb.202307035","DOIUrl":"10.1083/jcb.202307035","url":null,"abstract":"Preserving the health of the mitochondrial network is critical to cell viability and longevity. To do so, mitochondria employ several membrane remodeling mechanisms, including the formation of mitochondrial-derived vesicles (MDVs) and compartments (MDCs) to selectively remove portions of the organelle. In contrast to well-characterized MDVs, the distinguishing features of MDC formation and composition remain unclear. Here, we used electron tomography to observe that MDCs form as large, multilamellar domains that generate concentric spherical compartments emerging from mitochondrial tubules at ER-mitochondria contact sites. Time-lapse fluorescence microscopy of MDC biogenesis revealed that mitochondrial membrane extensions repeatedly elongate, coalesce, and invaginate to form these compartments that encase multiple layers of membrane. As such, MDCs strongly sequester portions of the outer mitochondrial membrane, securing membrane cargo into a protected domain, while also enclosing cytosolic material within the MDC lumen. Collectively, our results provide a model for MDC formation and describe key features that distinguish MDCs from other previously identified mitochondrial structures and cargo-sorting domains.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 11","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971159","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

A complex of the lipid transport ER proteins TMEM24 and C2CD2 with band 4.1 at cell-cell contacts. 脂质转运 ER 蛋白 TMEM24 和 C2CD2 与带 4.1 在细胞-细胞接触处的复合物。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-11-04 Epub Date: 2024-08-19 DOI: 10.1083/jcb.202311137

Ben Johnson, Maria Iuliano, TuKiet T Lam, Thomas Biederer, Pietro V De Camilli

引用次数: 0

Cyclin B3 is a dominant fast-acting cyclin that drives rapid early embryonic mitoses. 细胞周期蛋白 B3 是一种显性快速作用细胞周期蛋白，它能驱动早期胚胎的快速有丝分裂。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-11-04 Epub Date: 2024-08-06 DOI: 10.1083/jcb.202308034

Pablo Lara-Gonzalez, Smriti Variyar, Shabnam Moghareh, Anh Cao Ngoc Nguyen, Amrutha Kizhedathu, Jacqueline Budrewicz, Aleesa Schlientz, Neha Varshney, Andrew Bellaart, Karen Oegema, Lee Bardwell, Arshad Desai

{"title":"Cyclin B3 is a dominant fast-acting cyclin that drives rapid early embryonic mitoses.","authors":"Pablo Lara-Gonzalez, Smriti Variyar, Shabnam Moghareh, Anh Cao Ngoc Nguyen, Amrutha Kizhedathu, Jacqueline Budrewicz, Aleesa Schlientz, Neha Varshney, Andrew Bellaart, Karen Oegema, Lee Bardwell, Arshad Desai","doi":"10.1083/jcb.202308034","DOIUrl":"10.1083/jcb.202308034","url":null,"abstract":"Mitosis in early embryos often proceeds at a rapid pace, but how this pace is achieved is not understood. Here, we show that cyclin B3 is the dominant driver of rapid embryonic mitoses in the C. elegans embryo. Cyclins B1 and B2 support slow mitosis (NEBD to anaphase ∼600 s), but the presence of cyclin B3 dominantly drives the approximately threefold faster mitosis observed in wildtype. Multiple mitotic events are slowed down in cyclin B1 and B2-driven mitosis, and cyclin B3-associated Cdk1 H1 kinase activity is ∼25-fold more active than cyclin B1-associated Cdk1. Addition of cyclin B1 to fast cyclin B3-only mitosis introduces an ∼60-s delay between completion of chromosome alignment and anaphase onset; this delay, which is important for segregation fidelity, is dependent on inhibitory phosphorylation of the anaphase activator Cdc20. Thus, cyclin B3 dominance, coupled to a cyclin B1-dependent delay that acts via Cdc20 phosphorylation, sets the rapid pace and ensures mitotic fidelity in the early C. elegans embryo.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 11","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893507","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

Nesprin-2 coordinates opposing microtubule motors during nuclear migration in neurons. 神经元核迁移过程中，Nesprin-2 可协调对立的微管马达。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-11-04 Epub Date: 2024-08-08 DOI: 10.1083/jcb.202405032

Chuying Zhou, You Kure Wu, Fumiyoshi Ishidate, Takahiro K Fujiwara, Mineko Kengaku

{"title":"Nesprin-2 coordinates opposing microtubule motors during nuclear migration in neurons.","authors":"Chuying Zhou, You Kure Wu, Fumiyoshi Ishidate, Takahiro K Fujiwara, Mineko Kengaku","doi":"10.1083/jcb.202405032","DOIUrl":"10.1083/jcb.202405032","url":null,"abstract":"Nuclear migration is critical for the proper positioning of neurons in the developing brain. It is known that bidirectional microtubule motors are required for nuclear transport, yet the mechanism of the coordination of opposing motors is still under debate. Using mouse cerebellar granule cells, we demonstrate that Nesprin-2 serves as a nucleus-motor adaptor, coordinating the interplay of kinesin-1 and dynein. Nesprin-2 recruits dynein-dynactin-BicD2 independently of the nearby kinesin-binding LEWD motif. Both motor binding sites are required to rescue nuclear migration defects caused by the loss of function of Nesprin-2. In an intracellular cargo transport assay, the Nesprin-2 fragment encompassing the motor binding sites generates persistent movements toward both microtubule minus and plus ends. Nesprin-2 drives bidirectional cargo movements over a prolonged period along perinuclear microtubules, which advance during the migration of neurons. We propose that Nesprin-2 keeps the nucleus mobile by coordinating opposing motors, enabling continuous nuclear transport along advancing microtubules in migrating cells.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 11","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901862","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

Racing through C. elegans mitosis using cyclin B3. 利用细胞周期蛋白 B3 在秀丽隐杆线虫有丝分裂过程中飞驰。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-11-04 Epub Date: 2024-10-28 DOI: 10.1083/jcb.202410007

Andreas Boland, Julia Kamenz

引用次数: 0