Molecular Biology of the Cell最新文献

筛选
英文 中文
A large reverse-genetic screen identifies numerous regulators of testis nascent myotube collective cell migration and collective organ sculpting. 一个大的反向遗传筛选确定了睾丸新生肌管集体细胞迁移和集体器官雕刻的许多调节因子。
IF 3.1 3区 生物学
Molecular Biology of the Cell Pub Date : 2025-02-01 Epub Date: 2025-01-02 DOI: 10.1091/mbc.E24-10-0456
Maik C Bischoff, Jenevieve E Norton, Erika A Munguia, Sarah E Clark, Noah J Gurley, Rebecca Korankye, Emmanuel Addai Gyabaah, Taino Encarnacion, Christopher J Serody, Corbin D Jones, Mark Peifer
{"title":"A large reverse-genetic screen identifies numerous regulators of testis nascent myotube collective cell migration and collective organ sculpting.","authors":"Maik C Bischoff, Jenevieve E Norton, Erika A Munguia, Sarah E Clark, Noah J Gurley, Rebecca Korankye, Emmanuel Addai Gyabaah, Taino Encarnacion, Christopher J Serody, Corbin D Jones, Mark Peifer","doi":"10.1091/mbc.E24-10-0456","DOIUrl":"10.1091/mbc.E24-10-0456","url":null,"abstract":"<p><p>Collective cell migration is critical for morphogenesis, homeostasis, and wound healing. Migrating mesenchymal cells form tissues that shape the body's organs. We developed a powerful model, exploring how <i>Drosophila</i> nascent myotubes migrate onto the testis during pupal development, forming the muscles ensheathing it and creating its characteristic spiral shape. To define genes regulating this, we used RNA sequencing (RNA-seq) to identify genes expressed in myotubes during migration. Using this dataset, we curated a list of 131 ligands, receptors, and cytoskeletal regulators, including all Rho/Ras/Rap1 regulators, as candidates. We then expressed 279 short hairpin RNAs (shRNAs) targeting these genes and examined adult testes. We identified 29 genes with diverse roles in morphogenesis. Some have phenotypes consistent with defective migration, while others alter testis shape in different ways, revealing the underlying logic of testis morphogenesis. We followed up on the Rho-family GEF dPix in detail. dPix knockdown drastically reduced migration and thus muscle coverage. Our data suggest different isoforms of dPix play distinct roles in this process and reveal a role for its partner Git. We also explored whether dPix regulates Cdc42 activity or cell adhesion. Our RNA-seq dataset and genetic analysis provide an important resource for the community to explore cell migration and organ morphogenesis.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar21"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Bioelectricity is a universal multifaced signaling cue in living organisms.
IF 3.1 3区 生物学
Molecular Biology of the Cell Pub Date : 2025-02-01 DOI: 10.1091/mbc.E23-08-0312
GuangJun Zhang, Michael Levin
{"title":"Bioelectricity is a universal multifaced signaling cue in living organisms.","authors":"GuangJun Zhang, Michael Levin","doi":"10.1091/mbc.E23-08-0312","DOIUrl":"10.1091/mbc.E23-08-0312","url":null,"abstract":"<p><p>The cellular electrical signals of living organisms were discovered more than a century ago and have been extensively investigated in the neuromuscular system. Neuronal depolarization and hyperpolarization are essential for our neuromuscular physiological and pathological functions. Bioelectricity is being recognized as an ancient, intrinsic, fundamental property of all living cells, and it is not limited to the neuromuscular system. Instead, emerging evidence supports a view of bioelectricity as an instructional signaling cue for fundamental cellular physiology, embryonic development, regeneration, and human diseases, including cancers. Here, we highlight the current understanding of bioelectricity and share our views on the challenges and perspectives.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":"36 2","pages":"pe2"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
β-actin function in platelets and red blood cells can be performed by γ-actin and is therefore independent of actin isoform protein sequence. β-肌动蛋白在血小板和红细胞中的功能可由γ-肌动蛋白完成,因此与肌动蛋白异构体蛋白序列无关。
IF 3.1 3区 生物学
Molecular Biology of the Cell Pub Date : 2025-02-01 Epub Date: 2024-12-20 DOI: 10.1091/mbc.E24-04-0186
Devasmita Chakravarty, Pavan Vedula, Megan Coffin, Li Chen, Stephanie Sterling, Alina D Peshkova, Aae Suzuki, Liang Zhao, Katrick Patra, Charles-Antoine Assenmacher, Enrico Radaelli, Mark Levine, Rustem I Litvinov, Charles S Abrams, Velia M Fowler, Anna Kashina
{"title":"β-actin function in platelets and red blood cells can be performed by γ-actin and is therefore independent of actin isoform protein sequence.","authors":"Devasmita Chakravarty, Pavan Vedula, Megan Coffin, Li Chen, Stephanie Sterling, Alina D Peshkova, Aae Suzuki, Liang Zhao, Katrick Patra, Charles-Antoine Assenmacher, Enrico Radaelli, Mark Levine, Rustem I Litvinov, Charles S Abrams, Velia M Fowler, Anna Kashina","doi":"10.1091/mbc.E24-04-0186","DOIUrl":"10.1091/mbc.E24-04-0186","url":null,"abstract":"<p><p>Actin is an essential component of the cytoskeleton in every eukaryotic cell. β-and γ-nonmuscle actin are over 99% identical to each other at the protein level but are encoded by different genes and play distinct roles in vivo. Blood cells, especially red blood cells (RBC), contain almost exclusively β-actin, and it has been generally assumed that this bias is dictated by the unique suitability of β-actin for RBC cytoskeleton function due to its specific amino acid sequence. Here we tested this assumption by analyzing the \"β-coded γ-actin\" (Actbcg) mouse model, in which the β-actin gene is edited by five-point mutations to produce γ-actin protein. Strikingly, despite lacking β-actin protein, Actbcg mice had no detectable phenotypes in RBCs, and no changes in the RBC shape, integrity, deformability, and molecular composition of their spectrin-based membrane skeleton. No actin-dependent changes were observed in platelets, another anucleate cell type enriched for β-actin. Our data show that, contrary to expectations, β-actin function in mature RBCs and platelets is independent of its protein sequence and therefore its enrichment in hematopoiesis and mature blood cells is likely driven entirely by its nucleotide-dependent functions.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar18"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Ubiquitin-mediated recruitment of the ATG9A-ATG2 lipid transfer complex drives clearance of phosphorylated p62 aggregates. 泛素介导的ATG9A-ATG2脂质转移复合物的募集驱动磷酸化p62聚集体的清除。
IF 3.1 3区 生物学
Molecular Biology of the Cell Pub Date : 2025-02-01 Epub Date: 2024-12-24 DOI: 10.1091/mbc.E24-03-0101
David G Broadbent, Colten M McEwan, Dasun Jayatunge, Emily G Kaminsky, Tsz-Min Tsang, Daniel M Poole, Bradley C Naylor, John C Price, Jens C Schmidt, Josh L Andersen
{"title":"Ubiquitin-mediated recruitment of the ATG9A-ATG2 lipid transfer complex drives clearance of phosphorylated p62 aggregates.","authors":"David G Broadbent, Colten M McEwan, Dasun Jayatunge, Emily G Kaminsky, Tsz-Min Tsang, Daniel M Poole, Bradley C Naylor, John C Price, Jens C Schmidt, Josh L Andersen","doi":"10.1091/mbc.E24-03-0101","DOIUrl":"10.1091/mbc.E24-03-0101","url":null,"abstract":"<p><p>Autophagy is an essential cellular recycling process that maintains protein and organelle homeostasis. ATG9A vesicle recruitment is a critical early step in autophagy to initiate autophagosome biogenesis. The mechanisms of ATG9A vesicle recruitment are best understood in the context of starvation-induced nonselective autophagy, whereas less is known about the signals driving ATG9A vesicle recruitment to autophagy initiation sites in the absence of nutrient stress. Here we demonstrate that loss of ATG9A, or the lipid transfer protein ATG2, leads to the accumulation of phosphorylated p62 aggregates in nutrient replete conditions. Furthermore, we show that p62 degradation requires the lipid scramblase activity of ATG9A. Last, we present evidence that polyubiquitin is an essential signal that recruits ATG9A and mediates autophagy foci assembly in nutrient replete cells. Together, our data support a ubiquitin-driven model of ATG9A recruitment and autophagosome formation during basal autophagy.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar20"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Zelda is dispensable for Drosophila melanogaster histone gene regulation. Zelda对黑腹果蝇组蛋白基因调控是不可或缺的。
IF 3.1 3区 生物学
Molecular Biology of the Cell Pub Date : 2025-02-01 Epub Date: 2024-12-11 DOI: 10.1091/mbc.E24-01-0028
Tommy O'Haren, Tsutomu Aoki, Leila E Rieder
{"title":"Zelda is dispensable for <i>Drosophila melanogaster</i> histone gene regulation.","authors":"Tommy O'Haren, Tsutomu Aoki, Leila E Rieder","doi":"10.1091/mbc.E24-01-0028","DOIUrl":"10.1091/mbc.E24-01-0028","url":null,"abstract":"<p><p>To ensure that the embryo can package exponentially increasing amounts of DNA, replication-dependent histones are some of the earliest transcribed genes from the zygotic genome. However, how the histone genes are identified is not known. The <i>Drosophila melanogaster</i> pioneer factor CLAMP regulates the embryonic histone genes and helps establish the histone locus body, a suite of factors that controls histone mRNA biosynthesis, but CLAMP is not unique to the histone genes. Zelda collaborates with CLAMP across the genome to regulate zygotic genome activation and target early activated genes. We hypothesized that Zelda helps identify histone genes for early embryonic expression. We found that Zelda targets the histone gene locus early during embryogenesis, prior to histone gene expression. However, depletion of <i>zelda</i> in the early embryo does not affect histone mRNA levels or prevent the recruitment of other factors. These results suggest the earliest events responsible for specifying the zygotic histone genes remain undiscovered.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"br3"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
USP34 regulates endothelial PAR1 mRNA transcript expression and cellular signaling. USP34 可调节内皮 PAR1 mRNA 转录本的表达和细胞信号传导。
IF 3.1 3区 生物学
Molecular Biology of the Cell Pub Date : 2025-02-01 Epub Date: 2024-12-20 DOI: 10.1091/mbc.E24-07-0294
Norton Cheng, Monica Gonzalez Ramirez, Chloe Edwards, JoAnn Trejo
{"title":"USP34 regulates endothelial PAR1 mRNA transcript expression and cellular signaling.","authors":"Norton Cheng, Monica Gonzalez Ramirez, Chloe Edwards, JoAnn Trejo","doi":"10.1091/mbc.E24-07-0294","DOIUrl":"10.1091/mbc.E24-07-0294","url":null,"abstract":"<p><p>Signaling by G protein-coupled receptors (GPCRs) is regulated by temporally distinct processes including receptor desensitization, internalization, and lysosomal sorting, and are tightly controlled by posttranslational modifications. While the role of phosphorylation in regulating GPCR signaling is well studied and established, the mechanisms by which other posttranslational modifications, such as ubiquitination, regulate GPCR signaling are not clearly defined. We hypothesize that GPCR ubiquitination and deubiquitination is critical for proper signaling and cellular responses. In the present study, we show that the deubiquitinase ubiquitin-specific protease-34 (USP34) regulates thrombin-stimulated protease-activated receptor-1 (PAR1)-induced p38 autophosphorylation and activation. The PAR1-stimulated p38 signaling pathway is driven by ubiquitination. Interestingly, small interfering RNA-induced knockdown of USP34 expression markedly increased PAR1 cell surface abundance and protein expression without modulating PAR1 ubiquitination or the ubiquitination status of p38 signaling pathway components. In addition, increased PAR1 expression observed in USP34-depleted cells was not caused by altered PAR1 constitutive internalization, agonist-induced internalization, or receptor degradation. Rather, we report that loss of USP34 expression increased mRNA transcript expression of the PAR1-encoding gene, <i>F2R</i>. This study unexpectedly identified a critical role for USP34 in regulation of <i>F2R</i> mRNA transcript expression, which modulates PAR1 cell surface levels and thrombin-stimulated p38 mitogen-activated protein kinase signaling.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar12"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
TUDCA modulates drug bioavailability to regulate resistance to acute ER stress in Saccharomyces cerevisiae. TUDCA通过调节药物生物利用度来调节酿酒酵母对急性内质网应激的抗性。
IF 3.1 3区 生物学
Molecular Biology of the Cell Pub Date : 2025-02-01 Epub Date: 2024-12-11 DOI: 10.1091/mbc.E24-04-0147
Sarah R Chadwick, Samuel Stack-Couture, Matthew D Berg, Sonja Di Gregorio, Bryan Lung, Julie Genereaux, Robyn D Moir, Christopher J Brandl, Ian M Willis, Erik L Snapp, Patrick Lajoie
{"title":"TUDCA modulates drug bioavailability to regulate resistance to acute ER stress in <i>Saccharomyces cerevisiae</i>.","authors":"Sarah R Chadwick, Samuel Stack-Couture, Matthew D Berg, Sonja Di Gregorio, Bryan Lung, Julie Genereaux, Robyn D Moir, Christopher J Brandl, Ian M Willis, Erik L Snapp, Patrick Lajoie","doi":"10.1091/mbc.E24-04-0147","DOIUrl":"10.1091/mbc.E24-04-0147","url":null,"abstract":"<p><p>Cells counter accumulation of misfolded secretory proteins in the endoplasmic reticulum (ER) through activation of the Unfolded Protein Response (UPR). Small molecules termed chemical chaperones can promote protein folding to alleviate ER stress. The bile acid tauroursodeoxycholic acid (TUDCA) has been described as a chemical chaperone. While promising in models of protein folding diseases, TUDCA's mechanism of action remains unclear. Here, we found TUDCA can rescue growth of yeast treated with the ER stressor tunicamycin (Tm), even in the absence of a functional UPR. In contrast, TUDCA failed to rescue growth on other ER stressors. Nor could TUDCA attenuate chronic UPR associated with specific gene deletions or overexpression of a misfolded mutant secretory protein. Neither pretreatment with nor delayed addition of TUDCA conferred protection against Tm. Importantly, attenuation of Tm-induced toxicity required TUDCA's critical micelle forming concentration, suggesting a mechanism where TUDCA directly sequesters drugs. Indeed, in several assays, TUDCA-treated cells closely resembled cells treated with lower doses of Tm. In addition, we found TUDCA can inhibit dyes from labeling intracellular compartments. Thus, our study challenges the model of TUDCA as a chemical chaperone and suggests that TUDCA decreases drug bioavailability, allowing cells to adapt to ER stress.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar13"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Nonessential kinetochore proteins contribute to meiotic chromosome condensation through polo-like kinase. 非必要的动点核蛋白通过类波罗激酶促进减数分裂染色体的凝聚。
IF 3.1 3区 生物学
Molecular Biology of the Cell Pub Date : 2025-02-01 Epub Date: 2024-12-20 DOI: 10.1091/mbc.E24-08-0348
Deepika Trakroo, Prakhar Agarwal, Anushka Alekar, Santanu Kumar Ghosh
{"title":"Nonessential kinetochore proteins contribute to meiotic chromosome condensation through polo-like kinase.","authors":"Deepika Trakroo, Prakhar Agarwal, Anushka Alekar, Santanu Kumar Ghosh","doi":"10.1091/mbc.E24-08-0348","DOIUrl":"10.1091/mbc.E24-08-0348","url":null,"abstract":"<p><p>Chromosome condensation plays a pivotal role during faithful chromosome segregation, hence, understanding the factors that drive condensation is crucial to get mechanistic insight into chromosome segregation. Previously, we showed that in budding yeast, the absence of the nonessential kinetochore proteins affects chromatin-condensin association in meiosis but not in mitosis. A differential organization of the kinetochores, that we and others observed earlier during mitosis and meiosis may contribute to the meiotic-specific role. Here, with our in-depth investigation using in vivo chromosome condensation assays in cells lacking a nonessential kinetochore protein, Ctf19, we establish that these proteins have roles in achieving a higher meiotic condensation without influencing much of the mitotic condensation. We further observed an accumulation of the polo-like kinase Cdc5 owing to its higher protein stability in <i>ctf19Δ</i> meiotic cells. High Cdc5 activity causes hyperphosphorylation of the condensin resulting in its reduced stability and concomitant decreased association with the chromatin. Overall, our findings highlight the role of Ctf19 in promoting meiotic chromosome condensation by influencing the activity of Cdc5 and thereby affecting the stability and association of condensin with the chromatin.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar14"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
ZYG-12/Hook's dual role as a dynein adaptor for early endosomes and nuclei is regulated by alternative splicing of its cargo binding domain. ZYG-12/Hook作为早期核内体和细胞核的动力蛋白适配器的双重作用是通过其货物结合结构域的选择性剪接来调节的。
IF 3.1 3区 生物学
Molecular Biology of the Cell Pub Date : 2025-02-01 Epub Date: 2024-12-24 DOI: 10.1091/mbc.E24-08-0364
Cátia Carvalho, Matilde Moreira, Daniel J Barbosa, Fung-Yi Chan, Carlota Boal Koehnen, Vanessa Teixeira, Helder Rocha, Mattie Green, Ana Xavier Carvalho, Dhanya K Cheerambathur, Reto Gassmann
{"title":"ZYG-12/Hook's dual role as a dynein adaptor for early endosomes and nuclei is regulated by alternative splicing of its cargo binding domain.","authors":"Cátia Carvalho, Matilde Moreira, Daniel J Barbosa, Fung-Yi Chan, Carlota Boal Koehnen, Vanessa Teixeira, Helder Rocha, Mattie Green, Ana Xavier Carvalho, Dhanya K Cheerambathur, Reto Gassmann","doi":"10.1091/mbc.E24-08-0364","DOIUrl":"10.1091/mbc.E24-08-0364","url":null,"abstract":"<p><p>The microtubule motor cytoplasmic dynein-1 transports and positions various organelles, but the molecular basis of this functional diversity is not fully understood. Cargo adaptors of the Hook protein family recruit dynein to early endosomes (EE) in fungi and human cells by forming the FTS-Hook-FHIP (FHF) complex. By contrast, the <i>Caenorhabditis elegans</i> Hook homologue ZYG-12 recruits dynein to the nuclear envelope (NE) in the meiotic gonad and mitotic early embryo by forming a Linker of Nucleoskeleton and Cytoskeleton (LINC) complex. Here, we demonstrate that ZYG-12 recruits dynein to EE in epithelia. We identify and functionally characterize the homologues of FTS (UBC-19) and FHIP (FHIP-1) that constitute the <i>C. elegans</i> FHF complex, validate the predicted FHIP-1-RAB-5 binding interface in vivo, and show that ZYG-12 forms FHF via a conserved segment that precedes, and is distinct from, its C-terminal NE targeting domain. Finally, we show that C-terminal ZYG-12 splice isoforms differ in their ability to target to the NE and EE. We conclude that the <i>C. elegans</i> Hook adaptor evolved to recruit dynein to two distinct organelles, and that cargo specificity of ZYG-12 is regulated by alternative splicing.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar19"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Cryo-electron tomography of eel sperm flagella reveals a molecular "minimum system" for motile cilia. 鳗鱼精子鞭毛的低温电子断层扫描揭示了运动纤毛的分子“最小系统”。
IF 3.1 3区 生物学
Molecular Biology of the Cell Pub Date : 2025-02-01 Epub Date: 2024-12-11 DOI: 10.1091/mbc.E24-08-0351
Jason R Schrad, Gang Fu, Whitney E Hable, Alexandra M Tayar, Kenneth Oliveira, Daniela Nicastro
{"title":"Cryo-electron tomography of eel sperm flagella reveals a molecular \"minimum system\" for motile cilia.","authors":"Jason R Schrad, Gang Fu, Whitney E Hable, Alexandra M Tayar, Kenneth Oliveira, Daniela Nicastro","doi":"10.1091/mbc.E24-08-0351","DOIUrl":"10.1091/mbc.E24-08-0351","url":null,"abstract":"<p><p>Cilia and flagella play a crucial role in the development and function of eukaryotes. The activity of thousands of dyneins is precisely regulated to generate flagellar motility. The complex proteome (600+ proteins) and architecture of the structural core of flagella, the axoneme, have made it challenging to dissect the functions of the different complexes, like the regulatory machinery. Previous reports suggested that the flagellum of American eel sperm lacks many of the canonical axonemal complexes yet is still motile. Here, we use cryo-electron tomography for molecular characterization of this proposed \"minimal\" motile flagellum. We observed different diameters for the eel sperm flagellum: narrow at the base and wider toward the flagellar tip. Subtomogram averaging revealed the three-dimensional (3D) structure of the eel sperm flagellum. As expected, major complexes were missing, for example, outer dynein arms, radial spokes, and the central pair complex, but we found molecular remnants of most complexes. We also identified bend direction-specific patterns in the inter-DMT distance in actively beating eel sperm flagella and we propose a model for the regulation of dynein activity during their motility. Together, our results shed light on the structure and function of the eel sperm flagellum and provide insight into the minimum requirements for ciliary beating.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar15"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信