Journal of cell science最新文献

Phosphorylation-induced SUMOylation promotes Ulk4 condensation at the ciliary tip to transduce Hedgehog signal. 磷酸化诱导的SUMOylation促进Ulk4在纤毛尖端的缩聚，从而转导Hedgehog信号。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-10-15 Epub Date: 2025-05-19 DOI: 10.1242/jcs.263695

Mengmeng Zhou, Yuhong Han, Jin Jiang

{"title":"Phosphorylation-induced SUMOylation promotes Ulk4 condensation at the ciliary tip to transduce Hedgehog signal.","authors":"Mengmeng Zhou, Yuhong Han, Jin Jiang","doi":"10.1242/jcs.263695","DOIUrl":"10.1242/jcs.263695","url":null,"abstract":"Hedgehog (Hh) signaling controls embryonic development and adult tissue homeostasis through the Gli family of transcription factors. In vertebrates, Hh signal transduction depends on the primary cilium, where Gli proteins are thought to be activated at the ciliary tip, but the underlying mechanism has remained poorly understood. Here, we provide evidence that two Unc-51-like kinase (Ulk) family members, Stk36 and Ulk4, regulate Gli2 ciliary tip localization and activation through phosphorylation and SUMOylation-mediated condensation in response to the Hh family protein Shh. We find that Stk36-mediated phosphorylation of Ulk4 promotes its SUMOylation in response to Shh, and the subsequent interaction between SUMO and a SUMO-interacting-motif (SIM) in the C-terminal region of Ulk4 drives Ulk4 self-assembly to form biomolecular condensates that also recruit Stk36 and Gli2. SUMOylation or SIM-deficient Ulk4 failed to accumulate at ciliary tip to activate Gli2 whereas phospho-mimetic mutation of Ulk4 sufficed to drive Ulk4, Stk36 and Gli2 condensation at ciliary tip, leading to constitutive Shh pathway activation in a manner dependent on Ulk4 SUMOylation. Taken together, our results suggest that phosphorylation-dependent SUMOylation of Ulk4 promotes kinase-substrate condensation at ciliary tip to transduce the Hh signal.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Primary cilia shape postnatal astrocyte development through Sonic Hedgehog signaling. 初级纤毛通过Sonic Hedgehog信号影响出生后星形胶质细胞的发育。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-10-15 Epub Date: 2025-05-19 DOI: 10.1242/jcs.263965

Rachel Bear, Steven A Sloan, Tamara Caspary

{"title":"Primary cilia shape postnatal astrocyte development through Sonic Hedgehog signaling.","authors":"Rachel Bear, Steven A Sloan, Tamara Caspary","doi":"10.1242/jcs.263965","DOIUrl":"10.1242/jcs.263965","url":null,"abstract":"Primary cilia function as specialized signaling centers that regulate many cellular processes including neuron and glia development. Astrocytes possess cilia, but the function of cilia in astrocyte development remains largely unexplored. Crucially, dysfunction of either astrocytes or cilia contributes to the molecular changes observed in neurodevelopmental disorders. Here, we show that a subpopulation of developing astrocytes in the prefrontal cortex are ciliated. This population corresponds to proliferating astrocytes and largely expresses the ciliary protein ARL13B. Genetic ablation of astrocyte cilia in vivo at two distinct stages of astrocyte development results in changes to Sonic Hedgehog (Shh) transcriptional targets. We show that Shh activity is decreased in immature and mature astrocytes upon loss of cilia. Furthermore, loss of cilia in immature astrocytes results in decreased astrocyte proliferation and loss of cilia in mature astrocytes causes enlarged astrocyte morphology. Together, these results indicate that astrocytes require cilia for Shh signaling throughout development and uncover functions for astrocyte cilia in regulating astrocyte proliferation and maturation. This expands our fundamental knowledge of astrocyte development and cilia function to advance our understanding of neurodevelopmental disorders.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

SLC-25A46 regulates mitochondrial fusion through FZO-1/Mitofusin and is. SLC-25A46通过FZO-1/Mitofusin调控线粒体融合。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-30 DOI: 10.1242/jcs.263571

Hiroyuki Obinata, Taisei Watanabe, Hironori Takahashi, Satoshi Shimo, Toshiyuki Oda, Asako Sugimoto, Shinsuke Niwa

{"title":"SLC-25A46 regulates mitochondrial fusion through FZO-1/Mitofusin and is.","authors":"Hiroyuki Obinata, Taisei Watanabe, Hironori Takahashi, Satoshi Shimo, Toshiyuki Oda, Asako Sugimoto, Shinsuke Niwa","doi":"10.1242/jcs.263571","DOIUrl":"https://doi.org/10.1242/jcs.263571","url":null,"abstract":"Mitochondria are dynamic organelles shaped by sequential fission and fusion events. The mitochondrial protein SLC25A46 has been identified as a causative gene for mitochondrial neuropathies. However, the function of SLC25A46 in mitochondrial morphogenesis remains controversial, with several reports suggesting it acts as a mitochondrial fission factor, while others propose it as a fusion factor. In this study, employing forward genetics, we identified slc-25A46, a Caenorhabditis elegans orthologue of human SLC25A46, as an essential factor for mitochondrial fusion. Suppressor mutagenesis screening revealed loss-of-function mutations in drp-1, a mitochondrial fission factor, as suppressors of slc-25A46. The phenotype of slc-25A46 mutants is similar to that of fzo-1 mutants, wherein the mitochondrial fusion factor Mitofusin is disrupted. Overexpressing FZO-1/Mitofusin mitigated mitochondrial defects in slc-25a46 mutants, indicating SLC-25A46 promotes fusion through FZO-1/Mitofusin. Disease model worms carrying mutations associated with SLC25A46 exhibited mitochondrial fragmentation and accelerated neurodegeneration, suggesting slc-25A46 maintains neuronal morphology through mitochondrial fusion regulation.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Endosomal RFFL ubiquitin ligase regulates mitochondrial morphology by targeting Mitofusin 2. 内体RFFL泛素连接酶通过靶向Mitofusin 2调控线粒体形态。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-30 DOI: 10.1242/jcs.263830

Nikhil Dev Narendradev, Rishith Ravindran, Parul Jain, Shikha Chaudhary, Anoop Kumar G Velikkakath, Abyasree Sudharman, Adithya Janardhanan, Tapas Chandra Nag, Subhash Chandra Yadav, Srinivasa Murty Srinivasula

{"title":"Endosomal RFFL ubiquitin ligase regulates mitochondrial morphology by targeting Mitofusin 2.","authors":"Nikhil Dev Narendradev, Rishith Ravindran, Parul Jain, Shikha Chaudhary, Anoop Kumar G Velikkakath, Abyasree Sudharman, Adithya Janardhanan, Tapas Chandra Nag, Subhash Chandra Yadav, Srinivasa Murty Srinivasula","doi":"10.1242/jcs.263830","DOIUrl":"https://doi.org/10.1242/jcs.263830","url":null,"abstract":"Mitochondrial homeostasis is ensured through communication between diverse cellular organelles, including mitochondria, the endoplasmic reticulum (ER), lysosomes, and endosomes. While mitofusins regulate mitochondrial networks and ER contacts, their role in endosomal-mitochondrial interactions remains unclear. Previously, we reported that endosomal ubiquitin ligase, RFFL-positive vesicles are associated with damaged mitochondria and prime the organelle for PRKN recruitment. Now, we establish that RFFL is a ubiquitin ligase for MFN2. Using electron microscopy and confocal imaging analyses, we demonstrate that RFFL knockout cells exhibit enlarged mitochondrial morphology. RFFL interacts at an endogenous level with MFN2 and contributes to its ubiquitination upon mitochondrial damage. Recombinant RFFL interacts and ubiquitinates MFN2 protein in vitro. Furthermore, exogenous RFFL in a ligase-dependent manner specifically reduces the exogenous protein levels of both MFN1 and MFN2, but not that of DRP1, and also perturbs lipid homeostasis. Importantly, we show that hyperfused mitochondria morphology reported with expression of pathogenic disease mutants of MFN2 (T206I and R364W) of Charcot-Marie-Tooth disease type 2A can be rescued by RFFL co-expression. The study unravels novel mechanisms involving endosomal ubiquitin ligases in mitochondrial networks.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

A novel approach to tagging tubulin reveals MT assembly dynamics of the axoneme in Trypanosoma brucei. 一种标记微管蛋白的新方法揭示了布鲁氏锥虫轴突体的MT组装动力学。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-29 DOI: 10.1242/jcs.264145

Daniel Abbühl, Martina Pružincová, Luděk Štěpánek, Eleonore Bouscasse, Rita Azevedo, Mariette Matondo, Vladimir Varga, Serge Bonnefoy, Philippe Bastin

{"title":"A novel approach to tagging tubulin reveals MT assembly dynamics of the axoneme in Trypanosoma brucei.","authors":"Daniel Abbühl, Martina Pružincová, Luděk Štěpánek, Eleonore Bouscasse, Rita Azevedo, Mariette Matondo, Vladimir Varga, Serge Bonnefoy, Philippe Bastin","doi":"10.1242/jcs.264145","DOIUrl":"https://doi.org/10.1242/jcs.264145","url":null,"abstract":"The protozoan parasite Trypanosoma brucei assembles a new flagellum while maintaining the existing one in the same cell. Our group proposed a model where the mature flagellum is locked after construction to full length (Bertiaux et al. 2018). To test this hypothesis directly, we monitored flagellum assembly dynamics by inducible expression of tubulin, marked with an intragenic tag. We found that addition of new tubulin occurs at the distal flagellum tip at a linear rate and is indeed restricted to the new flagellum in bi-flagellated cells. Depleting the locking protein CEP164C prior to induction resulted in simultaneous integration of new tubulin in both flagella. This is direct evidence that trypanosomes avoid competition between the two flagella by allowing tubulin incorporation only in the new organelle. However, by tracing flagella over several cell cycles we also found that flagella do not remain locked forever. An orthogonal approach with HaloTag-tagged radial spoke protein 4/6 supported these findings. Since flagellum length in trypanosomes is stable, this indicates regular events of transient disassembly, followed by assembly, of the entire axoneme at the distal tip.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

SAXO proteins mediate tubulin turnover in axonemal microtubules of Chlamydomonas. SAXO蛋白介导衣藻轴突微管中的微管蛋白转换。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-27 DOI: 10.1242/jcs.264074

Yongli Zhang, Xuecheng Li, Zhengmao Wang, Junmin Pan

{"title":"SAXO proteins mediate tubulin turnover in axonemal microtubules of Chlamydomonas.","authors":"Yongli Zhang, Xuecheng Li, Zhengmao Wang, Junmin Pan","doi":"10.1242/jcs.264074","DOIUrl":"https://doi.org/10.1242/jcs.264074","url":null,"abstract":"Cilia and eukaryotic flagella are microtubule-based organelles crucial for cell motility and signaling. SAXO proteins (stabilizers of axonemal microtubules) are found exclusively in flagellated or ciliated organisms, but their physiological functions remain unclear. We investigated four SAXO proteins (SAXO1-4) in Chlamydomonas, identified via bioinformatics. All localize to cilia but differ in axonemal binding and spatial distribution. Single SAXO knockouts had no effect, while double mutants (saxo1/2, saxo1/3 and saxo2/3) showed shorter cilia. This phenotype intensified in the saxo1/2/3 triple mutant but not further in the quadruple mutant. Ciliary beating remained normal in saxo1/2/3 mutants, even under mechanical stress, indicating SAXO1-3 are not essential for ciliary rigidity. Biochemical and proteomic analyses revealed no significant changes in the ciliary proteome or in tubulin acetylation, tyrosination and glutamylation within cilia. However, dikaryon assays with labelled tubulin show increased axonemal tubulin turnover in saxo1/2/3 mutant. Our findings underscore a critical role of SAXO proteins in stabilizing axonemal microtubules by reducing tubulin turnover, thereby regulating ciliary length and assembly, and provide new insights into their function in cilia.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Skeletal ciliopathy variants of dynein-2 DYNC2LI1 subunit impair osteogenic differentiation of mesenchymal stem cells. 骨骼肌纤毛病动力蛋白-2 DYNC2LI1亚基变异损害间充质干细胞的成骨分化。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-21 DOI: 10.1242/jcs.263737

Yamato Ishida, Haruka Hoshi, Kenichi Kawano, Hye-Won Shin, Yohei Katoh, Kazuhisa Nakayama

{"title":"Skeletal ciliopathy variants of dynein-2 DYNC2LI1 subunit impair osteogenic differentiation of mesenchymal stem cells.","authors":"Yamato Ishida, Haruka Hoshi, Kenichi Kawano, Hye-Won Shin, Yohei Katoh, Kazuhisa Nakayama","doi":"10.1242/jcs.263737","DOIUrl":"https://doi.org/10.1242/jcs.263737","url":null,"abstract":"Skeletal ciliopathies result from defects in primary cilia, which are crucial for embryonic development through transduction of extracellular signals, including Hedgehog. Selective transport of ciliary proteins is mediated by the intraflagellar transport (IFT) machinery, containing the IFT-A and IFT-B complexes and the kinesin-2 and dynein-2 motors. Biallelic loss-of-function variants in genes encoding dynein-2-specific subunits, including DYNC2LI1, cause skeletal ciliopathies. As mesenchymal stem cells (MSCs) differentiate into osteoblasts, we investigated the effects of pathogenic variants of DYNC2LI1 on osteogenic differentiation of the MSC-like line C3H10T1/2. Dync2li1-knockout cells expressing disease-causing DYNC2LI1 variants demonstrated defects in the retrograde ciliary protein trafficking, including Hedgehog pathway GPCRs, Smoothened and GPR161. Furthermore, Dync2li1-knockout cells expressing the pathogenic variants demonstrated impaired Hedgehog signaling, in particular, a reduced ratio of the GLI3 repressor form to total GLI3, resulting in impaired osteogenic differentiation of MSCs. By contrast, osteogenic differentiation via BMP signaling was derepressed in Dync2li1-knockout cells. This suggests that skeletal ciliopathies caused by DYNC2LI1 variants could be attributable in part to impaired osteogenic differentiation due to defects in Hedgehog signaling, resulting from defects in retrograde ciliary protein trafficking.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

β-Arrestin mediates the export of ciliary GPR161 but not Smoothened together with the BBSome and IFT machinery. β- arrest介导睫状GPR161的输出，但不与BBSome和IFT机制一起平滑。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-19 DOI: 10.1242/jcs.263793

Taiju Fujii, Norihito Murai, Shinya Aso, Hiroyuki Takatsu, Hye-Won Shin, Yohei Katoh, Kazuhisa Nakayama

{"title":"β-Arrestin mediates the export of ciliary GPR161 but not Smoothened together with the BBSome and IFT machinery.","authors":"Taiju Fujii, Norihito Murai, Shinya Aso, Hiroyuki Takatsu, Hye-Won Shin, Yohei Katoh, Kazuhisa Nakayama","doi":"10.1242/jcs.263793","DOIUrl":"https://doi.org/10.1242/jcs.263793","url":null,"abstract":"Specific G protein-coupled receptors (GPCRs) exist on the ciliary membrane. Hedgehog signaling activation triggers the import of Smoothened into and export of GPR161 from cilia. The BBSome comprising eight Bardet-Biedl syndrome (BBS) proteins mediates GPCR export, together with the intraflagellar transport (IFT) machinery, containing the IFT-A and IFT-B complexes. The absence of any BBSome subunit or IFT27/BBS19 (IFT-B subunit) impairs ciliary GPCR export, including GPR161. Plasma membrane GPCRs undergo phosphorylation by GPCR kinases (GRKs) and subsequent binding of β-arrestins (β-arrestin1/ARRB1 and β-arrestin2/ARRB2), crucial for clathrin-mediated endocytosis. We here confirmed that GPR161 and β-arrestin are accumulated within cilia in the absence of IFT27 or the BBSome, and that ARRB1/ARRB2-double knockout impairs GPR161 export. Notably, we found that activation-mimetic β-arrestin mutants can interact with both the BBSome and ciliary GPCRs, and cause constitutive export of GPR161. Moreover, we demonstrated that GRK2 plays a crucial role in GPR161 export. We here propose that phosphorylated GPR161 recruits β-arrestins, converting them into their activated conformation. Activated β-arrestins then interact with the BBSome, which connects them to the IFT machinery to facilitate GPR161 export.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Glutamine modulates stress granule formation in cancer cells through core RNA-binding proteins. 谷氨酰胺通过核心rna结合蛋白调节癌细胞中的应激颗粒形成。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-16 DOI: 10.1242/jcs.263679

Gabriel P Faber, Gilad Gross, Oz Mualem, Matan Y Avivi, Hiba Waldman Ben-Asher, Orly Yaron, Orit Shefi, Rakefet Ben-Yishay, Dana Ishay-Ronen, Yaron Shav-Tal

{"title":"Glutamine modulates stress granule formation in cancer cells through core RNA-binding proteins.","authors":"Gabriel P Faber, Gilad Gross, Oz Mualem, Matan Y Avivi, Hiba Waldman Ben-Asher, Orly Yaron, Orit Shefi, Rakefet Ben-Yishay, Dana Ishay-Ronen, Yaron Shav-Tal","doi":"10.1242/jcs.263679","DOIUrl":"https://doi.org/10.1242/jcs.263679","url":null,"abstract":"Cytoplasmic stress granules (SGs) induced by various stresses have been linked to cancer and other disorders. Which active energy pathways are required for SG formation remains unclear. We used nutrient deprivation to show that glutamine is the sole amino acid source governing whether cancer cells form SGs. Metabolic profiling revealed the essential functions of glutamine and glucose in SG formation under limiting metabolic conditions. Providing glutamine during metabolic stress restored ATP levels in cancer cells and revived many essential gene expression patterns. Myc, a known regulator of the shift between glucose and glutamine metabolism, showed increased expression as cells moved to glutamine uptake. Inhibition of MYC prevented SG formation even with glutamine present and increased cell death after arsenite exposure. The RNA-binding proteins G3BP1/2 were required for glutamine utilization, with G3BP1/2 knockout cells displaying a heavier reliance on glucose, yielding reduced cell survival and inability to properly utilize glutamine. Altogether, we show that cancer cells require glutamine for SG formation under nutrient deprivation, and its absence reduces cell survival, lowering ATP levels below an energy threshold required for SG formation.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

A Cryo-Electron Microscopy structure of yeast Pex5 in complex with a cargo uncovers a novel binding interface. 酵母Pex5与货物复合物的低温电镜结构揭示了一个新的结合界面。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-16 DOI: 10.1242/jcs.263890

Lior Peer, Orly Dym, Nadav Elad, Asa Tirosh, Jossef Jacobovitch, Ehud Sivan, Mor Angel, Shira Albeck, Maya Schuldiner, Yoav Peleg, Einat Zalckvar

{"title":"A Cryo-Electron Microscopy structure of yeast Pex5 in complex with a cargo uncovers a novel binding interface.","authors":"Lior Peer, Orly Dym, Nadav Elad, Asa Tirosh, Jossef Jacobovitch, Ehud Sivan, Mor Angel, Shira Albeck, Maya Schuldiner, Yoav Peleg, Einat Zalckvar","doi":"10.1242/jcs.263890","DOIUrl":"https://doi.org/10.1242/jcs.263890","url":null,"abstract":"Proper protein targeting to organelles is crucial for maintaining eukaryotic cellular function and homeostasis. This necessity has driven the evolution of specific targeting signals on proteins and the targeting factors that recognize them. A prominent example is peroxisomal matrix proteins, most of which depend on the targeting factor Pex5 to localize and function correctly. While most Pex5 cargoes contain a Peroxisomal Targeting Signal type 1 (PTS1), they are not all targeted similarly. Some undergo priority targeting, facilitated either by stronger binding to specific subsets of PTS1 signals or by additional interaction interfaces. These observations highlight the extensive complexity of Pex5-mediated targeting. In this study, we reveal that the matrix protein Eci1 can reach peroxisomes and bind Pex5 in the absence of PTS1. By solving the structure of the yeast Pex5-Eci1 complex using Cryo-Electron Microscopy, we identified additional binding interfaces. Our findings provide new insights into the versatile interactions between Pex5 and its cargo, Eci1. More broadly, this work highlights the intricate, dynamic nature of the interactions between cargo factors and their cargoes to meet the complex environment within eukaryotic cells.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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