Journal of Cell Biology最新文献_第5页

TMBIM-2 orchestrates systemic mitochondrial stress response via facilitating Ca2+ oscillations. TMBIM-2通过促进Ca2+振荡协调全身性线粒体应激反应。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-05-05 Epub Date: 2025-03-18 DOI: 10.1083/jcb.202408050

Jiasheng Li, Jimeng Cui, Xinyu Li, Di Zhu, Zhenhua Chen, Xiahe Huang, Yingchun Wang, Qingfeng Wu, Ye Tian

{"title":"TMBIM-2 orchestrates systemic mitochondrial stress response via facilitating Ca2+ oscillations.","authors":"Jiasheng Li, Jimeng Cui, Xinyu Li, Di Zhu, Zhenhua Chen, Xiahe Huang, Yingchun Wang, Qingfeng Wu, Ye Tian","doi":"10.1083/jcb.202408050","DOIUrl":"10.1083/jcb.202408050","url":null,"abstract":"Neuronal mitochondrial function is critical for orchestrating inter-tissue communication essential for overall fitness. Despite its significance, the molecular mechanism underlying the impact of prolonged mitochondrial stresses on neuronal activity and how they orchestrate metabolism and aging remains elusive. Here, we identified the evolutionarily conserved transmembrane protein XBX-6/TMBIM-2 as a key mediator in the neuronal-to-intestinal mitochondrial unfolded protein response (UPRmt). Our investigations reveal that intrinsic neuronal mitochondrial stress triggers spatiotemporal Ca2+ oscillations in a TMBIM-2-dependent manner through the Ca2+ efflux pump MCA-3. Notably, persistent Ca2+ oscillations at synapses of ADF neurons are critical for facilitating serotonin release and the subsequent activation of the neuronal-to-intestinal UPRmt. TMBIM2 expression diminishes with age; however, its overexpression counteracts the age-related decline in aversive learning behavior and extends the lifespan of Caenorhabditis elegans. These findings underscore the intricate integration of chronic neuronal mitochondrial stress into neurotransmission processes via TMBIM-2-dependent Ca2+ equilibrium, driving metabolic adaptation and behavioral changes for the regulation of aging.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11917168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656728","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 pathway of unconventional protein secretion involves CUPS and a modified trans-Golgi network. 非常规蛋白分泌途径涉及CUPS和修饰的反式高尔基网络。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-05-05 Epub Date: 2025-02-27 DOI: 10.1083/jcb.202312120

Amy J Curwin, Kazuo Kurokawa, Gonzalo Bigliani, Nathalie Brouwers, Akihiko Nakano, Vivek Malhotra

{"title":"The pathway of unconventional protein secretion involves CUPS and a modified trans-Golgi network.","authors":"Amy J Curwin, Kazuo Kurokawa, Gonzalo Bigliani, Nathalie Brouwers, Akihiko Nakano, Vivek Malhotra","doi":"10.1083/jcb.202312120","DOIUrl":"10.1083/jcb.202312120","url":null,"abstract":"Compartment for unconventional protein secretion (CUPS), a compartment for secretion of signal sequence-lacking proteins, forms through COPI-independent extraction of membranes from early Golgi cisternae, lacks Golgi-specific glycosyltransferases, and requires phosphatidylinositol 4-phosphate (PI4P) for biogenesis, as well as phosphatidylinositol 3-phosphate for stability. Our findings demonstrate that Drs2, a PI4P effector from the trans-Golgi network (TGN), is essential for CUPS formation, specifically through its interaction with Rcy1, and Rcy1 is crucial for the unconventional secretion. Using 4D super-resolution confocal live imaging microscopy, we observed that CUPS interact with a modified TGN that contains Drs2 in addition to proteins Tlg2 and Snc2, which are necessary for membrane fusion. Notably, while CUPS remain stable, the modified TGN undergoes remodeling during the later stages of unconventional secretion. In summary, we suggest that CUPS and the modified TGN, without the function of COPII and COPI, participate in collecting and sorting unconventionally secreted proteins, reflecting the role of Golgi membranes in receiving cargo from the ER during conventional secretion.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11867701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523585","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

Rab GTPases are evolutionarily conserved signals mediating selective autophagy. Rab gtpase是介导选择性自噬的进化保守信号。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-05-05 Epub Date: 2025-04-08 DOI: 10.1083/jcb.202410150

Pengwei Zhao, Rui Tian, Dandan Song, Qi Zhu, Xianming Ding, Jianqin Zhang, Beibei Cao, Mengyuan Zhang, Yilu Xu, Jie Fang, Jieqiong Tan, Cong Yi, Hongguang Xia, Wei Liu, Wei Zou, Qiming Sun

{"title":"Rab GTPases are evolutionarily conserved signals mediating selective autophagy.","authors":"Pengwei Zhao, Rui Tian, Dandan Song, Qi Zhu, Xianming Ding, Jianqin Zhang, Beibei Cao, Mengyuan Zhang, Yilu Xu, Jie Fang, Jieqiong Tan, Cong Yi, Hongguang Xia, Wei Liu, Wei Zou, Qiming Sun","doi":"10.1083/jcb.202410150","DOIUrl":"10.1083/jcb.202410150","url":null,"abstract":"Selective autophagy plays a crucial role in maintaining cellular homeostasis by specifically targeting unwanted cargo labeled with \"autophagy cues\" signals for autophagic degradation. In this study, we identify Rab GTPases as a class of such autophagy cues signals involved in selective autophagy. Through biochemical and imaging screens, we reveal that human Rab GTPases are common autophagy substrates. Importantly, we confirm the conservation of Rab GTPase autophagic degradation in different model organisms. Rab GTPases translocate to damaged mitochondria, lipid droplets, and invading Salmonella-containing vacuoles (SCVs) to serve as degradation signals. Furthermore, they facilitate mitophagy, lipophagy, and xenophagy, respectively, by recruiting receptors. This interplay between Rab GTPases and receptors may ensure the de novo synthesis of isolation membranes around Rab-GTPase-labeled cargo, thereby mediating selective autophagy. These processes are further influenced by upstream regulators such as LRRK2, GDIs, and RabGGTase. In conclusion, this study unveils a conserved mechanism involving Rab GTPases as autophagy cues signals and proposes a model for the spatiotemporal control of selective autophagy.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803361","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: Chemical transformation of the multibudding yeast, Aureobasidium pullulans. 更正：多芽酵母的化学转化。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-05-05 Epub Date: 2025-04-10 DOI: 10.1083/jcb.20240211404042025c

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

引用次数: 0

PITPβ promotes COPI vesicle fission through lipid transfer and membrane contact formation. PITPβ通过脂质转移和膜接触形成促进COPI囊泡裂变。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-05-05 Epub Date: 2025-04-11 DOI: 10.1083/jcb.202407166

Kunyou Park, Sungeun Ju, Hyewon Choi, Peng Gao, Geul Bang, Jung Hoon Choi, Jiwon Jang, Andrew J Morris, Byung-Ho Kang, Victor W Hsu, Seung-Yeol Park

引用次数: 0

SNX10 functions as a modulator of piecemeal mitophagy and mitochondrial bioenergetics. SNX10作为片段线粒体自噬和线粒体生物能量学的调节剂。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-05-05 Epub Date: 2025-03-07 DOI: 10.1083/jcb.202404009

Laura Trachsel-Moncho, Chiara Veroni, Benan John Mathai, Ana Lapao, Sakshi Singh, Nagham Theres Asp, Sebastian W Schultz, Serhiy Pankiv, Anne Simonsen

引用次数: 0

Vacuoles provide the source membrane for TORC1-containing signaling endosomes. 液泡为含有torc1的信号内体提供源膜。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-05-05 Epub Date: 2025-03-07 DOI: 10.1083/jcb.202407021

Kenji Muneshige, Riko Hatakeyama

引用次数: 0

Rhythmic TDP-43 affects RNA splicing of USP13, resulting in alteration of BMAL1 ubiquitination. 节律性TDP-43影响USP13的RNA剪接，导致BMAL1泛素化的改变。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-05-05 Epub Date: 2025-04-09 DOI: 10.1083/jcb.202405142

Jianlan Gu, Mingming Yang, Liti Zhang, Yuxiao Liu, Ruolan Yan, Danmin Pan, Xiaowei Qian, Hanjing Hu, Dandan Chu, Chen Hu, Fei Liu, Hengxiang Cui

{"title":"Rhythmic TDP-43 affects RNA splicing of USP13, resulting in alteration of BMAL1 ubiquitination.","authors":"Jianlan Gu, Mingming Yang, Liti Zhang, Yuxiao Liu, Ruolan Yan, Danmin Pan, Xiaowei Qian, Hanjing Hu, Dandan Chu, Chen Hu, Fei Liu, Hengxiang Cui","doi":"10.1083/jcb.202405142","DOIUrl":"10.1083/jcb.202405142","url":null,"abstract":"Circadian rhythm disorders are common characteristics of neurodegenerative diseases. The pathological aggregation of transactive response DNA-binding protein 43 (TDP-43) is associated with multiple neurodegenerative diseases, such as amyotrophic lateral sclerosis. However, the relationship between TDP-43 and circadian rhythm remains unknown. Here, we found that TDP-43 is rhythmically expressed both in vivo and in vitro. TDP-43 knockdown affected the expression of circadian genes, including BMAL1, CLOCK, CRY1, and PER2, and impaired autonomous circadian wheel behavior, cognitive functions, and balance abilities in mice. Furthermore, TDP-43 knockdown induced aberrant splicing of ubiquitin-specific peptidase 13 (USP13) and blocked USP13 rhythmic expression, enhancing the ubiquitination of BMAL1. Meanwhile, TDP-43 knockdown altered the rhythmic expression of phospho-AMPKα (Thr172) and platelet-type phosphofructokinase (PFKP), which may change cellular glucose uptake and ATP production. Our findings further the understanding of the role of TDP-43 dysfunction in circadian rhythm disruption in neurodegenerative diseases and provide new mechanistic evidence supporting the interaction between circadian rhythm disruption and neurodegeneration.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811413","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 insights into the coupling between VCP, an essential unfoldase, and a deubiquitinase. VCP（一种基本展开酶）和去泛素酶之间耦合的结构见解。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-05-05 Epub Date: 2025-03-14 DOI: 10.1083/jcb.202410148

Lauren E Vostal, Noa E Dahan, Matthew J Reynolds, Lily I Kronenberg, Tarun M Kapoor

{"title":"Structural insights into the coupling between VCP, an essential unfoldase, and a deubiquitinase.","authors":"Lauren E Vostal, Noa E Dahan, Matthew J Reynolds, Lily I Kronenberg, Tarun M Kapoor","doi":"10.1083/jcb.202410148","DOIUrl":"10.1083/jcb.202410148","url":null,"abstract":"Proteostasis involves degradation and recycling of proteins from organelles, membranes, and multiprotein complexes. These processes can depend on protein extraction and unfolding by the essential mechanoenzyme valosin-containing protein (VCP) and on ubiquitin chain remodeling by ubiquitin-specific proteases known as deubiquitinases (DUBs). How the activities of VCP and DUBs are coordinated is poorly understood. Here, we focus on the DUB VCPIP1, a VCP interactor required for post-mitotic Golgi and ER organization. We determine ∼3.3 Å cryogenic electron microscopy structures of VCP-VCPIP1 complexes in the absence of added nucleotide or the presence of an ATP analog. We find that up to 3 VCPIP1 protomers interact with the VCP hexamer to position VCPIP1's catalytic domain at the exit of VCP's central pore, poised to cleave ubiquitin following substrate unfolding. We observe competition between VCPIP1 and other cofactors for VCP binding and show that VCP stimulates VCPIP1's DUB activity. Together, our data suggest how the two enzyme activities can be coordinated to regulate proteostasis.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624861","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 deubiquitinase USP45 inhibits autophagy through actin regulation by Coronin 1B. 去泛素化酶 USP45 通过 Coronin 1B 的肌动蛋白调节抑制自噬。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-05-05 Epub Date: 2025-03-11 DOI: 10.1083/jcb.202407014

Yuchieh Jay Lin, Li-Ting Huang, Po-Yuan Ke, Guang-Chao Chen

{"title":"The deubiquitinase USP45 inhibits autophagy through actin regulation by Coronin 1B.","authors":"Yuchieh Jay Lin, Li-Ting Huang, Po-Yuan Ke, Guang-Chao Chen","doi":"10.1083/jcb.202407014","DOIUrl":"10.1083/jcb.202407014","url":null,"abstract":"The autophagy-lysosomal system comprises a highly dynamic and interconnected vesicular network that plays a central role in maintaining proteostasis and cellular homeostasis. In this study, we uncovered the deubiquitinating enzyme (DUB), dUsp45/USP45, as a key player in regulating autophagy and lysosomal activity in Drosophila and mammalian cells. Loss of dUsp45/USP45 results in autophagy activation and increased levels of V-ATPase to lysosomes, thus enhancing lysosomal acidification and function. Furthermore, we identified the actin-binding protein Coronin 1B (Coro1B) as a substrate of USP45. USP45 interacts with and deubiquitinates Coro1B, thereby stabilizing Coro1B levels. Notably, the ablation of USP45 or Coro1B promotes the formation of F-actin patches and the translocation of V-ATPase to lysosomes in an N-WASP-dependent manner. Additionally, we observed positive effects of dUsp45 depletion on extending lifespan and ameliorating polyglutamine (polyQ)-induced toxicity in Drosophila. Our findings highlight the important role of dUsp45/USP45 in regulating lysosomal function by modulating actin structures through Coro1B.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605058","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