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Mitochondrial mayhem: Disrupting conserved N-terminal motifs in TANGO2 impacts its localization and function. 线粒体混乱：破坏 TANGO2 的保守 N 端基团会影响其定位和功能。
IF 7.8 1区 生物学
Journal of Cell Biology Pub Date : 2025-04-15 DOI: 10.1083/jcb.202503010
Sarah E Sandkuhler,Samuel J Mackenzie
{"title":"Mitochondrial mayhem: Disrupting conserved N-terminal motifs in TANGO2 impacts its localization and function.","authors":"Sarah E Sandkuhler,Samuel J Mackenzie","doi":"10.1083/jcb.202503010","DOIUrl":"https://doi.org/10.1083/jcb.202503010","url":null,"abstract":"TANGO2 deficiency in humans leads to progressive neurological impairment, punctuated by life-threatening metabolic crises. In this issue, Lujan and colleagues demonstrate that TANGO2 localizes within the mitochondrial lumen and binds acyl-CoA species, potentially implicating it as a lipid trafficking protein.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"27 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836604","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
Rab GTPases as "eat me" signals for selective autophagy. Rab GTPases是选择性自噬的 "吃我 "信号。
IF 7.8 1区 生物学
Journal of Cell Biology Pub Date : 2025-04-10 DOI: 10.1083/jcb.202502030
Yan G Zhao
{"title":"Rab GTPases as \"eat me\" signals for selective autophagy.","authors":"Yan G Zhao","doi":"10.1083/jcb.202502030","DOIUrl":"https://doi.org/10.1083/jcb.202502030","url":null,"abstract":"Selective autophagy targets specific cellular cargo for degradation. In this issue, Zhao et al. (https://doi.org/10.1083/jcb.202410150) uncovered that Rab GTPases serve as pivotal \"autophagy cues\" for recruitment of cargo receptors to facilitate mitophagy, lipophagy, and xenophagy, contributing to the precise spatiotemporal regulation of selective autophagy.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"106 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819160","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
Subversion of the host endocytic pathway by Legionella pneumophila-mediated ubiquitination of Rab5. 嗜肺军团菌介导的Rab5泛素化对宿主内吞途径的颠覆。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-04-07 Epub Date: 2025-03-04 DOI: 10.1083/jcb.202406159
Shino Tanaka, Hiromu Oide, Shumma Ikeda, Mitsuo Tagaya, Hiroki Nagai, Tomoko Kubori, Kohei Arasaki
{"title":"Subversion of the host endocytic pathway by Legionella pneumophila-mediated ubiquitination of Rab5.","authors":"Shino Tanaka, Hiromu Oide, Shumma Ikeda, Mitsuo Tagaya, Hiroki Nagai, Tomoko Kubori, Kohei Arasaki","doi":"10.1083/jcb.202406159","DOIUrl":"10.1083/jcb.202406159","url":null,"abstract":"<p><p>Legionella pneumophila is an intracellular bacterial pathogen that modulates membrane trafficking to survive and proliferate within host cells. After phagocytosis, the L. pneumophila-containing vacuole evades the endocytic pathway by excluding the host GTPase Rab5, a crucial regulator of phagosomal maturation. In this study, we show that the evolutionarily conserved lysine residue K134 of Rab5 undergoes ubiquitination during infection. This modification depends on Lpg2525, an F-box protein from L. pneumophila that acts as a component of the SKP-Cullin-F-box complex. We further demonstrate that Rab5 ubiquitination facilitates the recruitment of RabGAP-5, a Rab5-specific GAP, leading to Rab5 inactivation and subsequent release from the bacterial vacuole. Importantly, the K134 Rab5 mutant limits L. pneumophila replication within host cells. These findings reveal that Lpg2525-mediated Rab5 ubiquitination is a key survival strategy employed by L. pneumophila in infected host cells.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 4","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541835","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
Translation of unspliced retroviral genomic RNA in the host cell is regulated in both space and time. 宿主细胞中未剪接的逆转录病毒基因组 RNA 的翻译在空间和时间上都受到调控。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-04-07 Epub Date: 2025-01-27 DOI: 10.1083/jcb.202405075
Felipe Leon-Diaz, Célia Chamontin, Sébastien Lainé, Marius Socol, Edouard Bertrand, Marylène Mougel
{"title":"Translation of unspliced retroviral genomic RNA in the host cell is regulated in both space and time.","authors":"Felipe Leon-Diaz, Célia Chamontin, Sébastien Lainé, Marius Socol, Edouard Bertrand, Marylène Mougel","doi":"10.1083/jcb.202405075","DOIUrl":"10.1083/jcb.202405075","url":null,"abstract":"<p><p>Retroviruses carry a genomic intron-containing RNA with a long structured 5'-untranslated region, which acts either as a genome encapsidated in the viral progeny or as an mRNA encoding the key structural protein, Gag. We developed a single-molecule microscopy approach to simultaneously visualize the viral mRNA and the nascent Gag protein during translation directly in the cell. We found that a minority of the RNA molecules serve as mRNA and that they are translated in a fast and efficient process. Surprisingly, viral polysomes were also observed at the cell periphery, indicating that translation is regulated in both space and time. Virus translation near the plasma membrane may benefit from reduced competition for ribosomes with most cellular cytoplasmic mRNAs. In addition, local and efficient translation must spare energy to produce Gag proteins, where they accumulate to assemble new viral particles, potentially allowing the virus to evade the host's antiviral defenses.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 4","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046922","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
Any1 is a phospholipid scramblase involved in endosome biogenesis. Any1 是一种磷脂扰乱酶，参与内质体的生物生成。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-04-07 Epub Date: 2025-03-06 DOI: 10.1083/jcb.202410013
Jieqiong Gao, Rico Franzkoch, Cristian Rocha-Roa, Olympia Ekaterini Psathaki, Michael Hensel, Stefano Vanni, Christian Ungermann
{"title":"Any1 is a phospholipid scramblase involved in endosome biogenesis.","authors":"Jieqiong Gao, Rico Franzkoch, Cristian Rocha-Roa, Olympia Ekaterini Psathaki, Michael Hensel, Stefano Vanni, Christian Ungermann","doi":"10.1083/jcb.202410013","DOIUrl":"10.1083/jcb.202410013","url":null,"abstract":"<p><p>Endosomes are central organelles in the recycling and degradation of receptors and membrane proteins. Once endocytosed, such proteins are sorted at endosomes into intraluminal vesicles (ILVs). The resulting multivesicular bodies (MVBs) then fuse with the lysosomes, leading to the degradation of ILVs and recycling of the resulting monomers. However, the biogenesis of MVBs requires a constant lipid supply for efficient ILV formation. An ER-endosome membrane contact site has been suggested to play a critical role in MVB biogenesis. Here, we identify Any1 as a novel phospholipid scramblase, which functions with the lipid transfer protein Vps13 in MVB biogenesis. We uncover that Any1 cycles between the early endosomes and the Golgi and colocalizes with Vps13, possibly at a here-discovered potential contact site between lipid droplets (LDs) and endosomes. Strikingly, both Any1 and Vps13 are required for MVB formation, presumably to couple lipid flux with membrane homeostasis during ILV formation and endosome maturation.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 4","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567218","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
Cytoplasmic ribosomes on mitochondria alter the local membrane environment for protein import. 线粒体上的细胞质核糖体改变了蛋白质输入的局部膜环境。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-04-07 Epub Date: 2025-03-06 DOI: 10.1083/jcb.202407110
Ya-Ting Chang, Benjamin A Barad, Juliette Hamid, Hamidreza Rahmani, Brian M Zid, Danielle A Grotjahn
{"title":"Cytoplasmic ribosomes on mitochondria alter the local membrane environment for protein import.","authors":"Ya-Ting Chang, Benjamin A Barad, Juliette Hamid, Hamidreza Rahmani, Brian M Zid, Danielle A Grotjahn","doi":"10.1083/jcb.202407110","DOIUrl":"10.1083/jcb.202407110","url":null,"abstract":"<p><p>Most of the mitochondria proteome is nuclear-encoded, synthesized by cytoplasmic ribosomes, and targeted to the mitochondria posttranslationally. However, a subset of mitochondrial-targeted proteins is imported co-translationally, although the molecular mechanisms governing this process remain unclear. We employ cellular cryo-electron tomography to visualize interactions between cytoplasmic ribosomes and mitochondria in Saccharomyces cerevisiae. We use surface morphometrics tools to identify a subset of ribosomes optimally oriented on mitochondrial membranes for protein import. This allows us to establish the first subtomogram average structure of a cytoplasmic ribosome at the mitochondrial surface in the native cellular context, which showed three distinct connections with the outer mitochondrial membrane surrounding the peptide exit tunnel. Further, this analysis demonstrated that cytoplasmic ribosomes primed for mitochondrial protein import cluster on the outer mitochondrial membrane at sites of local constrictions of the outer and inner mitochondrial membranes. Overall, our study reveals the architecture and the spatial organization of cytoplasmic ribosomes at the mitochondrial surface, providing a native cellular context to define the mechanisms that mediate efficient mitochondrial co-translational protein import.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 4","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567220","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 unexpected structure and dynamics of vimentin networks. vimentin网络的意外结构和动态。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-04-07 Epub Date: 2025-03-18 DOI: 10.1083/jcb.202503012
Komal Bhattacharyya, Stefan Klumpp
{"title":"The unexpected structure and dynamics of vimentin networks.","authors":"Komal Bhattacharyya, Stefan Klumpp","doi":"10.1083/jcb.202503012","DOIUrl":"10.1083/jcb.202503012","url":null,"abstract":"<p><p>Bhattacharyya and Klumpp discuss exciting new observations of the native intermediate filament network in cells shown in Renganathan et al. (https://doi.org/10.1083/jcb.202406054) in this issue. Combining two powerful imaging techniques, Renganathan et al. examine the organization and dynamics of vimentin filaments in unprecedented detail.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 4","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11917166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656640","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
Centriole structural integrity defects are a crucial feature of hydrolethalus syndrome. 中心粒结构完整性缺陷是足部积水综合征的一个重要特征。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-04-07 Epub Date: 2025-02-26 DOI: 10.1083/jcb.202403022
Ana Curinha, Zhaoyu Huang, Taylor Anglen, Margaret A Strong, Colin R Gliech, Cayla E Jewett, Anoek Friskes, Thao P Phan, Zachary Nicholas, Andrew J Holland
{"title":"Centriole structural integrity defects are a crucial feature of hydrolethalus syndrome.","authors":"Ana Curinha, Zhaoyu Huang, Taylor Anglen, Margaret A Strong, Colin R Gliech, Cayla E Jewett, Anoek Friskes, Thao P Phan, Zachary Nicholas, Andrew J Holland","doi":"10.1083/jcb.202403022","DOIUrl":"10.1083/jcb.202403022","url":null,"abstract":"<p><p>Hydrolethalus syndrome (HLS) is a lethal, autosomal recessive ciliopathy caused by the mutation of the conserved centriole protein HYLS1. How HYLS1 controls centriole function is poorly understood. Here, we show that mice harboring the HYLS1 disease mutation die shortly after birth and exhibit developmental defects that recapitulate several manifestations of HLS. These phenotypes arise from a loss of centriole integrity that causes tissue-specific defects in cilia assembly and function. We show that HYLS1 is recruited to the centriole by CEP120 and stabilizes the localization of centriole inner scaffold proteins that ensure the integrity of the centriolar microtubule wall. The HLS disease mutation reduced the centriole localization of HYLS1 and caused degeneration of the centriole distal end. We propose that tissue-specific defects in centriole integrity caused by the HYLS1 mutation prevent ciliogenesis and contribute to HLS phenotypes.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 4","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143501412","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 LC3-interacting region of NBR1 is a protein interaction hub enabling optimal flux. NBR1的lc3相互作用区是一个蛋白质相互作用枢纽，可实现最佳通量。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-04-07 Epub Date: 2025-02-10 DOI: 10.1083/jcb.202407105
Brian J North, Amelia E Ohnstad, Michael J Ragusa, Christopher J Shoemaker
{"title":"The LC3-interacting region of NBR1 is a protein interaction hub enabling optimal flux.","authors":"Brian J North, Amelia E Ohnstad, Michael J Ragusa, Christopher J Shoemaker","doi":"10.1083/jcb.202407105","DOIUrl":"10.1083/jcb.202407105","url":null,"abstract":"<p><p>During autophagy, toxic cargo is encapsulated by autophagosomes and trafficked to lysosomes for degradation. NBR1, an autophagy receptor targeting ubiquitinated aggregates, serves as a model for studying the multivalent, heterotypic interactions of cargo-bound receptors. Here, we find that three critical NBR1 partners-ATG8-family proteins, FIP200, and TAX1BP1-each bind to distinct, overlapping determinants within a short linear interaction motif (SLiM). To explore whether overlapping SLiMs extend beyond NBR1, we analyzed >100 LC3-interacting regions (LIRs), revealing that FIP200 and/or TAX1BP1 binding to LIRs is a common phenomenon and suggesting LIRs as protein interaction hotspots. Phosphomimetic peptides demonstrate that phosphorylation generally enhances FIP200 and ATG8-family binding but not TAX1BP1, indicating differential regulation. In vivo, LIR-mediated interactions with TAX1BP1 promote optimal NBR1 flux by leveraging additional functionalities from TAX1BP1. These findings reveal a one-to-many binding modality in the LIR motif of NBR1, illustrating the cooperative mechanisms of autophagy receptors and the regulatory potential of multifunctional SLiMs.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 4","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382578","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
Structure of the F-tractin-F-actin complex. 牵拉蛋白-肌动蛋白复合物的结构。
IF 7.4 1区 生物学
Journal of Cell Biology Pub Date : 2025-04-07 Epub Date: 2025-02-10 DOI: 10.1083/jcb.202409192
Dmitry Shatskiy, Athul Sivan, Roland Wedlich-Söldner, Alexander Belyy
{"title":"Structure of the F-tractin-F-actin complex.","authors":"Dmitry Shatskiy, Athul Sivan, Roland Wedlich-Söldner, Alexander Belyy","doi":"10.1083/jcb.202409192","DOIUrl":"10.1083/jcb.202409192","url":null,"abstract":"<p><p>F-tractin is a peptide widely used to visualize the actin cytoskeleton in live eukaryotic cells but has been reported to impair cell migration and induce actin bundling at high expression levels. To elucidate these effects, we determined the cryo-EM structure of the F-tractin-F-actin complex, revealing that F-tractin consists of a flexible N-terminal region and an amphipathic C-terminal helix. The N-terminal part is dispensable for F-actin binding but responsible for the bundling effect. Based on these insights, we developed an optimized F-tractin, which eliminates the N-terminal region and minimizes bundling while retaining strong actin labeling. The C-terminal helix interacts with a hydrophobic pocket formed by two neighboring actin subunits, an interaction region shared by many actin-binding polypeptides, including the popular actin-binding probe Lifeact. Thus, rather than contrasting F-tractin and Lifeact, our data indicate that these peptides have analogous modes of interaction with F-actin. Our study dissects the structural elements of F-tractin and provides a foundation for developing future actin probes.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 4","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382573","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
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