Journal of Cell Biology最新文献_第8页

Integrated stress response activator halofuginone protects mice from diabetes-like phenotypes. 综合应激反应激活剂卤夫酮可保护小鼠免受糖尿病样表型的影响。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-10-07 Epub Date: 2024-08-16 DOI: 10.1083/jcb.202405175

Shashank Rai, Maria Szaruga, Aleksandra P Pitera, Anne Bertolotti

引用次数: 0

An evolutionarily conserved AnkyrinG-dependent motif clusters axonal K2P K+ channels. 轴突 K2P K+ 通道的一个进化保守的 AnkyrinG 依赖性基团。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-10-07 Epub Date: 2024-07-30 DOI: 10.1083/jcb.202401140

Gabriel Escobedo, Yu Wu, Yuki Ogawa, Xiaoyun Ding, Matthew N Rasband

{"title":"An evolutionarily conserved AnkyrinG-dependent motif clusters axonal K2P K+ channels.","authors":"Gabriel Escobedo, Yu Wu, Yuki Ogawa, Xiaoyun Ding, Matthew N Rasband","doi":"10.1083/jcb.202401140","DOIUrl":"10.1083/jcb.202401140","url":null,"abstract":"The evolution of ion channel clustering at nodes of Ranvier enabled the development of complex vertebrate nervous systems. At mammalian nodes, the K+ leak channels TRAAK and TREK-1 underlie membrane repolarization. Despite the molecular similarities between nodes and the axon initial segment (AIS), TRAAK and TREK-1 are reportedly node-specific, suggesting a unique clustering mechanism. However, we show that TRAAK and TREK-1 are enriched at both nodes and AIS through a common mechanism. We identified a motif near the C-terminus of TRAAK that is necessary and sufficient for its clustering. The motif first evolved among cartilaginous fish. Using AnkyrinG (AnkG) conditional knockout mice, CRISPR/Cas9-mediated disruption of AnkG, co-immunoprecipitation, and surface recruitment assays, we show that TRAAK forms a complex with AnkG and that AnkG is necessary for TRAAK's AIS and nodal clustering. In contrast, TREK-1's clustering requires TRAAK. Our results expand the repertoire of AIS and nodal ion channel clustering mechanisms and emphasize AnkG's central role in assembling excitable domains.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 10","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11289519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792525","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

Synaptotagmin-1 undergoes phase separation to regulate its calcium-sensitive oligomerization. 突触表蛋白-1通过相分离来调节其钙敏感性寡聚。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-10-07 Epub Date: 2024-07-09 DOI: 10.1083/jcb.202311191

Min Zhu, Han Xu, Yulei Jin, Xiaoxu Kong, Bingkuan Xu, Yinghui Liu, Haijia Yu

{"title":"Synaptotagmin-1 undergoes phase separation to regulate its calcium-sensitive oligomerization.","authors":"Min Zhu, Han Xu, Yulei Jin, Xiaoxu Kong, Bingkuan Xu, Yinghui Liu, Haijia Yu","doi":"10.1083/jcb.202311191","DOIUrl":"10.1083/jcb.202311191","url":null,"abstract":"Synaptotagmin-1 (Syt1) is a calcium sensor that regulates synaptic vesicle fusion in synchronous neurotransmitter release. Syt1 interacts with negatively charged lipids and the SNARE complex to control the fusion event. However, it remains incompletely understood how Syt1 mediates Ca2+-trigged synaptic vesicle fusion. Here, we discovered that Syt1 undergoes liquid-liquid phase separation (LLPS) to form condensates both in vitro and in living cells. Syt1 condensates play a role in vesicle attachment to the PM and efficiently recruit SNAREs and complexin, which may facilitate the downstream synaptic vesicle fusion. We observed that Syt1 condensates undergo a liquid-to-gel-like phase transition, reflecting the formation of Syt1 oligomers. The phase transition can be blocked or reversed by Ca2+, confirming the essential role of Ca2+ in Syt1 oligomer disassembly. Finally, we showed that the Syt1 mutations causing Syt1-associated neurodevelopmental disorder impair the Ca2+-driven phase transition. These findings reveal that Syt1 undergoes LLPS and a Ca2+-sensitive phase transition, providing new insights into Syt1-mediated vesicle fusion.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 10","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11232894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558843","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

LYSMD proteins promote activation of Rab32-family GTPases for lysosome-related organelle biogenesis. LYSMD蛋白可促进Rab32家族GTP酶的活化，从而促进溶酶体相关细胞器的生物生成。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-10-07 Epub Date: 2024-07-30 DOI: 10.1083/jcb.202402016

Jinglin Li, Qiuyuan Yin, Nan Xuan, Qiwen Gan, Chaolian Liu, Qian Zhang, Mei Yang, Chonglin Yang

{"title":"LYSMD proteins promote activation of Rab32-family GTPases for lysosome-related organelle biogenesis.","authors":"Jinglin Li, Qiuyuan Yin, Nan Xuan, Qiwen Gan, Chaolian Liu, Qian Zhang, Mei Yang, Chonglin Yang","doi":"10.1083/jcb.202402016","DOIUrl":"10.1083/jcb.202402016","url":null,"abstract":"Lysosome-related organelles (LROs) are specialized lysosomes with cell type-specific roles in organismal homeostasis. Dysregulation of LROs leads to many human disorders, but the mechanisms underlying their biogenesis are not fully understood. Here, we identify a group of LYSMD proteins as evolutionarily conserved regulators of LROs. In Caenorhabditis elegans, mutations of LMD-2, a LysM domain-containing protein, reduce the levels of the Rab32 GTPase ortholog GLO-1 on intestine-specific LROs, the gut granules, leading to their abnormal enlargement and defective biogenesis. LMD-2 interacts with GLO-3, a subunit of GLO-1 guanine nucleotide exchange factor (GEF), thereby promoting GLO-1 activation. Mammalian homologs of LMD-2, LYSMD1, and LYSMD2 can functionally replace LMD-2 in C. elegans. In mammals, LYSMD1/2 physically interact with the HPS1 subunit of BLOC-3, the GEF of Rab32/38, thus promoting Rab32 activation. Inactivation of both LYSMD1 and LYSMD2 reduces Rab32 activation, causing melanosome enlargement and decreased melanin production in mouse melanoma cells. These findings provide important mechanistic insights into LRO biogenesis and functions.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 10","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11289520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792526","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

Small GTPase ActIvitY ANalyzing (SAIYAN) system: A method to detect GTPase activation in living cells. 小 GTPase 活性分析（SAIYAN）系统：一种检测活细胞中 GTP 酶活化的方法。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-10-07 Epub Date: 2024-08-05 DOI: 10.1083/jcb.202403179

Miharu Maeda, Masashi Arakawa, Yukie Komatsu, Kota Saito

{"title":"Small GTPase ActIvitY ANalyzing (SAIYAN) system: A method to detect GTPase activation in living cells.","authors":"Miharu Maeda, Masashi Arakawa, Yukie Komatsu, Kota Saito","doi":"10.1083/jcb.202403179","DOIUrl":"10.1083/jcb.202403179","url":null,"abstract":"Small GTPases are essential in various cellular signaling pathways, and detecting their activation within living cells is crucial for understanding cellular processes. The current methods for detecting GTPase activation using fluorescent proteins rely on the interaction between the GTPase and its effector. Consequently, these methods are not applicable to factors, such as Sar1, where the effector also functions as a GTPase-activating protein. Here, we present a novel method, the Small GTPase ActIvitY ANalyzing (SAIYAN) system, for detecting the activation of endogenous small GTPases via fluorescent signals utilizing a split mNeonGreen system. We demonstrated Sar1 activation at the endoplasmic reticulum (ER) exit site and successfully detected its activation state in various cellular conditions. Utilizing the SAIYAN system in collagen-secreting cells, we discovered activated Sar1 localized both at the ER exit sites and ER-Golgi intermediate compartment (ERGIC) regions. Additionally, impaired collagen secretion confined the activated Sar1 at the ER exit sites, implying the importance of Sar1 activation through the ERGIC in collagen secretion.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 10","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889350","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

Permanent deconstruction of intracellular primary cilia in differentiating granule cell neurons. 分化中的颗粒细胞神经元细胞内原始纤毛的永久性解构

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-10-07 Epub Date: 2024-08-13 DOI: 10.1083/jcb.202404038

Carolyn M Ott, Sandii Constable, Tri M Nguyen, Kevin White, Wei-Chung Allen Lee, Jennifer Lippincott-Schwartz, Saikat Mukhopadhyay

{"title":"Permanent deconstruction of intracellular primary cilia in differentiating granule cell neurons.","authors":"Carolyn M Ott, Sandii Constable, Tri M Nguyen, Kevin White, Wei-Chung Allen Lee, Jennifer Lippincott-Schwartz, Saikat Mukhopadhyay","doi":"10.1083/jcb.202404038","DOIUrl":"10.1083/jcb.202404038","url":null,"abstract":"Primary cilia on granule cell neuron progenitors in the developing cerebellum detect sonic hedgehog to facilitate proliferation. Following differentiation, cerebellar granule cells become the most abundant neuronal cell type in the brain. While granule cell cilia are essential during early developmental stages, they become infrequent upon maturation. Here, we provide nanoscopic resolution of cilia in situ using large-scale electron microscopy volumes and immunostaining of mouse cerebella. In many granule cells, we found intracellular cilia, concealed from the external environment. Cilia were disassembled in differentiating granule cell neurons-in a process we call cilia deconstruction-distinct from premitotic cilia resorption in proliferating progenitors. In differentiating granule cells, cilia deconstruction involved unique disassembly intermediates, and, as maturation progressed, mother centriolar docking at the plasma membrane. Unlike ciliated neurons in other brain regions, our results show the deconstruction of concealed cilia in differentiating granule cells, which might prevent mitogenic hedgehog responsiveness. Ciliary deconstruction could be paradigmatic of cilia removal during differentiation in other tissues.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 10","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975791","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

Murine glial protrusion transcripts predict localized Drosophila glial mRNAs involved in plasticity. 小鼠神经胶质突起转录本预测了果蝇神经胶质 mRNA 的定位，这些 mRNA 与可塑性有关。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-10-07 Epub Date: 2024-07-22 DOI: 10.1083/jcb.202306152

Jeffrey Y Lee, Dalia S Gala, Maria Kiourlappou, Julia Olivares-Abril, Jana Joha, Joshua S Titlow, Rita O Teodoro, Ilan Davis

{"title":"Murine glial protrusion transcripts predict localized Drosophila glial mRNAs involved in plasticity.","authors":"Jeffrey Y Lee, Dalia S Gala, Maria Kiourlappou, Julia Olivares-Abril, Jana Joha, Joshua S Titlow, Rita O Teodoro, Ilan Davis","doi":"10.1083/jcb.202306152","DOIUrl":"10.1083/jcb.202306152","url":null,"abstract":"The polarization of cells often involves the transport of specific mRNAs and their localized translation in distal projections. Neurons and glia are both known to contain long cytoplasmic processes, while localized transcripts have only been studied extensively in neurons, not glia, especially in intact nervous systems. Here, we predict 1,740 localized Drosophila glial transcripts by extrapolating from our meta-analysis of seven existing studies characterizing the localized transcriptomes and translatomes of synaptically associated mammalian glia. We demonstrate that the localization of mRNAs in mammalian glial projections strongly predicts the localization of their high-confidence Drosophila homologs in larval motor neuron-associated glial projections and are highly statistically enriched for genes associated with neurological diseases. We further show that some of these localized glial transcripts are specifically required in glia for structural plasticity at the nearby neuromuscular junction synapses. We conclude that peripheral glial mRNA localization is a common and conserved phenomenon and propose that it is likely to be functionally important in disease.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 10","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11262410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734187","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

Chemical transformation of the multibudding yeast, Aureobasidium pullulans. 多芽酵母 Aureobasidium pullulans 的化学转化。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-10-07 Epub Date: 2024-06-27 DOI: 10.1083/jcb.202402114

Alison C E Wirshing, Claudia A Petrucco, Daniel J Lew

{"title":"Chemical transformation of the multibudding yeast, Aureobasidium pullulans.","authors":"Alison C E Wirshing, Claudia A Petrucco, Daniel J Lew","doi":"10.1083/jcb.202402114","DOIUrl":"10.1083/jcb.202402114","url":null,"abstract":"Aureobasidium pullulans is a ubiquitous polymorphic black yeast with industrial and agricultural applications. It has recently gained attention amongst cell biologists for its unconventional mode of proliferation in which multinucleate yeast cells make multiple buds within a single cell cycle. Here, we combine a chemical transformation method with genome-targeted homologous recombination to yield ∼60 transformants/μg of DNA in just 3 days. This protocol is simple, inexpensive, and requires no specialized equipment. We also describe vectors with codon-optimized green and red fluorescent proteins for A. pullulans and use these tools to explore novel cell biology. Quantitative imaging of a strain expressing cytosolic and nuclear markers showed that although the nuclear number varies considerably among cells of similar volume, total nuclear volume scales with cell volume over an impressive 70-fold size range. The protocols and tools described here expand the toolkit for A. pullulans biologists and will help researchers address the many other puzzles posed by this polyextremotolerant and morphologically plastic organism.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 10","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141457102","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

Lipid synthesis leads the way for invasive migration. 脂质合成是入侵迁移的先导。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-10-07 Epub Date: 2024-09-30 DOI: 10.1083/jcb.202408005

Laura M Machesky

引用次数: 0

VPS13B is localized at the interface between Golgi cisternae and is a functional partner of FAM177A1. VPS13B 定位于高尔基体细胞间的界面，是 FAM177A1 的功能伙伴。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2024-09-27 DOI: 10.1083/jcb.202311189

Berrak Ugur,Florian Schueder,Jimann Shin,Michael G Hanna,Yumei Wu,Marianna Leonzino,Maohan Su,Anthony R McAdow,Catherine Wilson,John Postlethwait,Lilianna Solnica-Krezel,Joerg Bewersdorf,Pietro De Camilli

{"title":"VPS13B is localized at the interface between Golgi cisternae and is a functional partner of FAM177A1.","authors":"Berrak Ugur,Florian Schueder,Jimann Shin,Michael G Hanna,Yumei Wu,Marianna Leonzino,Maohan Su,Anthony R McAdow,Catherine Wilson,John Postlethwait,Lilianna Solnica-Krezel,Joerg Bewersdorf,Pietro De Camilli","doi":"10.1083/jcb.202311189","DOIUrl":"https://doi.org/10.1083/jcb.202311189","url":null,"abstract":"Mutations in VPS13B, a member of a protein family implicated in bulk lipid transport between adjacent membranes, cause Cohen syndrome. VPS13B is known to be concentrated in the Golgi complex, but its precise location within this organelle and thus the site(s) where it achieves lipid transport remains unclear. Here, we show that VPS13B is localized at the interface between proximal and distal Golgi subcompartments and that Golgi complex reformation after Brefeldin A (BFA)-induced disruption is delayed in VPS13B KO cells. This delay is phenocopied by the loss of FAM177A1, a Golgi complex protein of unknown function reported to be a VPS13B interactor and whose mutations also result in a developmental disorder. In zebrafish, the vps13b ortholog, not previously annotated in this organism, genetically interacts with fam177a1. Collectively, these findings raise the possibility that bulk lipid transport by VPS13B may play a role in the dynamics of Golgi membranes and that VPS13B may be assisted in this function by FAM177A1.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"42 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142329095","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