Molecular Biology of the Cell最新文献_第10页

Tetraspanin CD82 regulates transforming growth factor-β signaling in hematopoietic stem and progenitor cells. Tetraspanin CD82在造血干细胞和祖细胞中调控转化生长因子β信号。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2025-07-01 Epub Date: 2025-05-28 DOI: 10.1091/mbc.E24-10-0474

Erica Pascetti, Muskan Floren, Tatiane da Silva Fernandes, Carina Anastasio, Levi Doyle, Jennifer Gillette

{"title":"Tetraspanin CD82 regulates transforming growth factor-β signaling in hematopoietic stem and progenitor cells.","authors":"Erica Pascetti, Muskan Floren, Tatiane da Silva Fernandes, Carina Anastasio, Levi Doyle, Jennifer Gillette","doi":"10.1091/mbc.E24-10-0474","DOIUrl":"10.1091/mbc.E24-10-0474","url":null,"abstract":"The cellular demand of the hematopoietic system is maintained by a rare pool of tissue-specific, hematopoietic stem cells (HSC). HSCs are primarily maintained in a quiescent state but can be activated to exit quiescence and undergo self-renewal and differentiation in response to stress. The cytokine transforming growth factor-β (TGF-β) plays an essential role in supporting HSC quiescence and activation, as one of the most potent inhibitors of hematopoietic stem and progenitor cell (HSPC) growth. Therefore, how TGF-β signaling can be regulated in the context of HSCs is of significant interest as it may uncover novel mechanisms to target HSC activity. Previous studies revealed that the tetraspanin CD82 modulates the long-term HSC population, with CD82 knockout (KO) mice displaying increased HSC activation. Here, in this study, we connect the CD82 scaffold with the regulation of TGF-β signaling in HSPCs. We show that CD82KO leads to decreased TGF-β signaling, whereas increased CD82 expression promotes TGF-β activation. These changes in CD82-mediated TGF-β signaling are associated with extracellular matrix interactions, as fibronectin engagement is critical for promoting TGF-β signaling. Mechanistically, we find that CD82 stimulates enhanced TGF-β activation by promoting receptor cross-talk between TGF-β receptor I and integrin β1, resulting in downstream changes in cell proliferation. Collectively, these findings demonstrate that CD82 modulates canonical TGF-β signaling through receptor cross-talk mechanisms that may be targeted to alter the balance between HSC quiescence and activation.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"br19"},"PeriodicalIF":3.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173992","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

Cell-cycle-regulated transcriptional pausing of Drosophila replication-dependent histone genes. 果蝇复制依赖组蛋白基因的细胞周期调控的转录暂停。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2025-07-01 Epub Date: 2025-05-21 DOI: 10.1091/mbc.E25-05-0212

James P Kemp, Mark S Geisler, Mia Hoover, Chun-Yi Cho, Patrick H O'Farrell, William F Marzluff, Robert J Duronio

{"title":"Cell-cycle-regulated transcriptional pausing of Drosophila replication-dependent histone genes.","authors":"James P Kemp, Mark S Geisler, Mia Hoover, Chun-Yi Cho, Patrick H O'Farrell, William F Marzluff, Robert J Duronio","doi":"10.1091/mbc.E25-05-0212","DOIUrl":"10.1091/mbc.E25-05-0212","url":null,"abstract":"Coordinated expression of replication-dependent (RD) histones genes occurs within the Histone Locus Body (HLB) during S-phase, but the molecular steps in transcription that are cell-cycle regulated are unknown. We report that Drosophila RNA Pol II promotes HLB formation and is enriched in the HLB outside of S-phase, including G1-arrested cells that do not transcribe RD histone genes. In contrast, the transcription elongation factor Spt6 is enriched in HLBs only during S-phase. Proliferating cells in the wing and eye primordium express full-length histone mRNAs during S-phase but express only short nascent transcripts in cells in G1 or G2 consistent with these transcripts being paused and then terminated. Full-length transcripts are produced when Cyclin E/Cdk2 is activated as cells enter S-phase. Thus, activation of transcription elongation by Cyclin E/Cdk2 and not recruitment of RNA pol II to the HLB is the critical step that links histone gene expression to cell-cycle progression.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar88"},"PeriodicalIF":3.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120277","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

Ulp1 association with nuclear pore complexes is required for the maintenance of global SUMOylation. Ulp1与核孔复合物的结合是维持整体sumo化所必需的。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2025-07-01 Epub Date: 2025-05-06 DOI: 10.1091/mbc.E24-12-0563

Christopher Ptak, Natasha O Saik, Richard W Wozniak

{"title":"Ulp1 association with nuclear pore complexes is required for the maintenance of global SUMOylation.","authors":"Christopher Ptak, Natasha O Saik, Richard W Wozniak","doi":"10.1091/mbc.E24-12-0563","DOIUrl":"10.1091/mbc.E24-12-0563","url":null,"abstract":"The SUMOylation state of a protein depends upon antagonistic SUMO conjugation and deconjugation activities that, in Saccharomyces cerevisiae, are primarily driven by the PIAS SUMO E3 ligases Siz1 and Siz2 and the SUMO isopeptidase Ulp1. Subcellular localization of these regulators determines where and when protein SUMOylation occurs. Ulp1 localizes at the nuclear basket of nuclear pore complexes (NPC), placing it at the interface of the nuclear periphery and the nucleoplasm; locales where most cellular SUMO-dependent processes occur. In cells lacking the nuclear basket component Nup60, we find that Ulp1/NPC association becomes temperature-dependent, and Ulp1/NPC dissociation at higher temperatures leads to Ulp1 proteasomal degradation. Ulp1 dissociation from NPC nuclear baskets also induces a signal that triggers Siz1 and Siz2 proteasomal degradation in a manner-dependent upon SUMOylation, SUMO chain assembly, and Ubc4-dependent ubiquitination. Ultimately, Siz protein degradation decreases cellular SUMOylation, and this reduction appears to promote cell viability under conditions where the association of Ulp1 with NPC nuclear baskets is perturbed. These observations suggest that SUMO homeostasis functions to regulate SUMO conjugate levels in direct proportion to Ulp1 levels at NPC nuclear baskets by modulating stability of the PIAS SUMO E3 ligases.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar81"},"PeriodicalIF":3.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044403","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

Live-cell painting: Image-based profiling in live cells using acridine orange. 活细胞绘画：使用吖啶橙对活细胞进行基于图像的分析。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2025-07-01 Epub Date: 2025-05-06 DOI: 10.1091/mbc.E24-07-0308

Fernanda Garcia-Fossa, Thaís Moraes-Lacerda, Mariana Rodrigues-da-Silva, Barbara Diaz-Rohrer, Shantanu Singh, Anne E Carpenter, Beth A Cimini, Marcelo Bispo de Jesus

{"title":"Live-cell painting: Image-based profiling in live cells using acridine orange.","authors":"Fernanda Garcia-Fossa, Thaís Moraes-Lacerda, Mariana Rodrigues-da-Silva, Barbara Diaz-Rohrer, Shantanu Singh, Anne E Carpenter, Beth A Cimini, Marcelo Bispo de Jesus","doi":"10.1091/mbc.E24-07-0308","DOIUrl":"10.1091/mbc.E24-07-0308","url":null,"abstract":"Image-based profiling has been used to analyze cell health, drug mechanism of action, CRISPR-edited cells, and overall cytotoxicity. Cell Painting is a broadly used image-based assay that uses morphological features to capture how cells respond to treatments. However, this method requires cell fixation for staining, which prevents examining live cells. To address this limitation, here we present Live-Cell Painting (LCP), a high-content method based on acridine orange, a metachromatic dye that labels different organelles and cellular structures. We began by showing that LCP can be applied to follow acidic vesicle redistribution of cells exposed to acidic vesicles inhibitors. Next, we show that LCP can identify subtle changes in cells exposed to silver nanoparticles that are not detected by techniques such as MTT assay. In drug treatments, LCP was helpful in assessing the dose-response relationship and creating profiles that allow clustering of drugs that cause liver injury. Here, we present an affordable and easy-to-use image-based assay capable of assessing overall cell health and showing promise for use in various applications such as assessing drugs and nanoparticles. We envisage the use of LCP as an initial screening of overall cell health while providing insights into new biological questions.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"mr7"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027284","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

Coordinated roles of the CEP164 homodimer and TTBK2 are required for recruitment of the IFT machinery to the mother centriole for ciliogenesis. CEP164同型二聚体和TTBK2的协同作用是将IFT机制招募到纤毛发生的母中心粒所必需的。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2025-07-01 Epub Date: 2025-04-30 DOI: 10.1091/mbc.E24-12-0536

Kohei Mori, Shingo Yamazaki, Kosei Yoshida, Rin Shirota, Shuhei Chiba, Hye-Won Shin, Yohei Katoh, Kazuhisa Nakayama

{"title":"Coordinated roles of the CEP164 homodimer and TTBK2 are required for recruitment of the IFT machinery to the mother centriole for ciliogenesis.","authors":"Kohei Mori, Shingo Yamazaki, Kosei Yoshida, Rin Shirota, Shuhei Chiba, Hye-Won Shin, Yohei Katoh, Kazuhisa Nakayama","doi":"10.1091/mbc.E24-12-0536","DOIUrl":"10.1091/mbc.E24-12-0536","url":null,"abstract":"Primary cilia are composed of axonemal microtubules that extend from the mother centriole-derived basal body and are sheathed by the ciliary membrane. Distal appendages (DAP) of the mother centriole play crucial roles as a scaffold to initiate ciliogenesis. Although previous studies indicated that the DAP proteins CEP164 and Tau-tubulin kinase 2 (TTBK2) participate in key events of ciliogenesis, including removal of CP110 from the mother centriole and recruitment of the intraflagellar transport (IFT) machinery to the mother centriole, the overall process involving these DAP proteins remains unclear. We here established CEP164-knockout (KO) and TTBK2-KO cells, and expressed various CEP164 and TTBK2 constructs in these cells. Our results showed that the interaction of TTBK2 with CEP164 and TTBK2 kinase activity is required for the recruitment of IFT machinery components (IFT-A, IFT-B, and dynein-2 complexes) to, and removal of CP110 from the mother centriole. However, CP110 removal is not always coupled with IFT protein recruitment. Analysis using chimeric constructs of CEP164 and TTBK2 indicated that CEP164 homodimerization via its central coiled-coil region is necessary for its mother centriole localization and subsequent TTBK2 recruitment, which are required for the recruitment of IFT machinery components to the mother centriole to trigger ciliogenesis.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar79"},"PeriodicalIF":3.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019771","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

Deep proteomic profiling of the intra-Golgi trafficking intermediates. 高尔基转运中间体的深层蛋白质组学分析。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2025-07-01 Epub Date: 2025-05-21 DOI: 10.1091/mbc.E24-12-0556

Farhana Taher Sumya, Walter S Aragon-Ramirez, Vladimir V Lupashin

{"title":"Deep proteomic profiling of the intra-Golgi trafficking intermediates.","authors":"Farhana Taher Sumya, Walter S Aragon-Ramirez, Vladimir V Lupashin","doi":"10.1091/mbc.E24-12-0556","DOIUrl":"10.1091/mbc.E24-12-0556","url":null,"abstract":"Intracellular trafficking relies on small membrane intermediates that transport cargo between different compartments. However, the precise role of vesicles in preserving Golgi function remains uncertain. To clarify this, we induced acute inactivation of the Conserved Oligomeric Golgi (COG) complex and analyzed vesicles from the different Golgi compartments. Proteomic analysis of the resulting vesicles revealed distinct molecular profiles, indicating a robust recycling system for Golgi proteins. All glycosylation enzymes and sugar transporters were detected in immunoisolated vesicles. The abundance of glycosylation machinery in intra-Golgi vesicles significantly increased following acute COG malfunction. Vesicles isolated from wild-type cells retained various vesicular coats, which were detaching from COG complex-dependent (CCD) vesicles stalled in the untethered state. Additionally, COG depletion led to increased molecular overlap among different populations of vesicles, suggesting that defects in vesicle tethering disrupt intra-Golgi sorting. Notably, CCD vesicles were functional and could be specifically rerouted to mitochondria that ectopically express Golgi tethers. Our findings demonstrate that the entire Golgi glycosylation machinery recycles within vesicles in a COG-dependent manner, whereas secretory and ER-Golgi trafficking proteins were not enriched. These results support a model in which the COG complex orchestrates the multistep recycling of glycosylation machinery, coordinated by specific coats, tethers, and SNAREs.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar87"},"PeriodicalIF":3.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120288","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

VAC14 oligomerization is essential for the function of the FAB1/PIKfyve-VAC14-FIG4 complex. VAC14寡聚化对于FAB1/PIKfyve-VAC14-FIG4复合物的功能至关重要。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2025-07-01 Epub Date: 2025-04-30 DOI: 10.1091/mbc.E24-11-0490

Li Zhang, Tunahan Uygun, Hye Jee Hahn, Yejun Liu, Pilar Rivero-Ríos, Dazhi Li, Vikas Navratna, Emily Bristow, Guangming Luo, Anna Kovarzin, Yuxia Bo, Suresh Gadde, Marceline Côté, Dennis C Ko, Shyamal Mosalaganti, Karin M Reinisch, Lois S Weisman

{"title":"VAC14 oligomerization is essential for the function of the FAB1/PIKfyve-VAC14-FIG4 complex.","authors":"Li Zhang, Tunahan Uygun, Hye Jee Hahn, Yejun Liu, Pilar Rivero-Ríos, Dazhi Li, Vikas Navratna, Emily Bristow, Guangming Luo, Anna Kovarzin, Yuxia Bo, Suresh Gadde, Marceline Côté, Dennis C Ko, Shyamal Mosalaganti, Karin M Reinisch, Lois S Weisman","doi":"10.1091/mbc.E24-11-0490","DOIUrl":"10.1091/mbc.E24-11-0490","url":null,"abstract":"The PIKfyve-VAC14-FIG4 complex synthesizes and turns over phosphatidylinositol-3,5-bisphosphate, PI(3,5)P2, an essential signaling lipid. A medium-resolution structure revealed that VAC14 forms a star-shaped pentamer scaffold. Two legs of VAC14 bind FIG4, with one leg also occupied by PIKfyve. The significance of VAC14 oligomerization was unknown. Here, using Alphafold2 and cryogenic electron microscopy maps we generated an atomic-resolution prediction, and found that some mutations linked to pediatric neurodegenerative diseases reside in the VAC14-VAC14 interfaces. A corresponding yeast mutation, along with additional mutations, demonstrates that VAC14 oligomerization is critical for Fab1/PIKfyve function. These mutations cause defects in the generation of PI(3,5)P2, in VAC14 localization, and in VAC14 oligomerization. Similarly, VAC14 patient mutations expressed in human VAC14 knockout (KO) cells, are defective in the formation of the PIKfyve-VAC14-FIG4 complex, as measured by pull-down assays, are defective in VAC14 oligomerization as measured by fluorescence-detection size-exclusion chromatography of cell lysates, and are defective in colocalization with VPS35-containing endosomes. These studies show that VAC14 oligomerization plays a crucial role in the regulation of PIKfyve/FAB1 and provide insights into selected patient mutations. Moreover, they suggest that small molecules that stabilize the VAC14 complex may provide an intervention for diseases linked to mutations in VAC14.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar78"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018562","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

Correction for Article Title "The laforin-malin complex, involved in Lafora disease, promotes the incorporation of K63-linked ubiquitin chains into AMP-activated protein kinase beta subunits". 更正文章标题“与拉福拉病有关的拉福拉素-马林复合物促进k63连接的泛素链并入amp激活的蛋白激酶β亚基”。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2025-07-01 DOI: 10.1091/mbc.E10-03-0227-corr

引用次数: 0

Membrane order regulates clathrin-coated pit dynamics but not initiation. 膜序调节网格蛋白包覆坑动力学，但不调节起始。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2025-07-01 Epub Date: 2025-04-30 DOI: 10.1091/mbc.E25-02-0081

G Aditya Kumar, Yousef Bagheri, Manojkumar A Puthenveedu

{"title":"Membrane order regulates clathrin-coated pit dynamics but not initiation.","authors":"G Aditya Kumar, Yousef Bagheri, Manojkumar A Puthenveedu","doi":"10.1091/mbc.E25-02-0081","DOIUrl":"10.1091/mbc.E25-02-0081","url":null,"abstract":"Clathrin-mediated endocytosis involves the remodeling of membranes via the initiation, maturation, and scission of clathrin-coated pits (CCPs). How CCP initiation and dynamics are regulated has been addressed primarily from the perspective of the core proteins that mediate endocytosis. Whether and how the physical properties of the membrane regulate CCP initiation and dynamics are heavily underexplored. Here, we used a solvatochromic probe to readout membrane order in the plasma membrane in live cells undergoing endocytosis, using total internal reflection fluorescence microscopy. Cholesterol depletion decreased membrane order, and reduced CCP initiation and increased lifetimes of CCPs. In unperturbed cells, however, membrane order was correlated to CCP lifetimes, but not their initiation. When membrane order was decreased or increased independently without extracting lipids, CCP lifetimes were affected, but CCP initiation was not. Together, by reading out membrane order in living cells undergoing endocytosis and manipulating membrane order in both directions, we show that membrane order primarily regulates CCP dynamics, and that cholesterol extraction has additional effects on CCP initiation independent of its effect on order.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"br17"},"PeriodicalIF":3.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023803","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

Regulation of misfolded protein aggregation and degradation by SUMOylation in budding yeast. 出芽酵母中SUMOylation对错误折叠蛋白聚集和降解的调控。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2025-07-01 Epub Date: 2025-04-30 DOI: 10.1091/mbc.E24-12-0540

Austin Folger, Emily Gutierrez-Morton, Marie-Helene Kabbaj, Mark Tyler Campbell, Garret Morton, Timothy L Megraw, Yanchang Wang

{"title":"Regulation of misfolded protein aggregation and degradation by SUMOylation in budding yeast.","authors":"Austin Folger, Emily Gutierrez-Morton, Marie-Helene Kabbaj, Mark Tyler Campbell, Garret Morton, Timothy L Megraw, Yanchang Wang","doi":"10.1091/mbc.E24-12-0540","DOIUrl":"10.1091/mbc.E24-12-0540","url":null,"abstract":"Protein misfolding is linked to many neurodegenerative disorders, such as Huntington's disease. The increase of glutamine-encoding CAG repeats in the first exon of huntingtin (HTT) causes Huntington's disease. Protein fragments of Htt exon 1 with polyQ expansion (mutant HTT, mHtt) are prone to aggregation, resulting in oligomers, amyloid fibrils, or large inclusion bodies. Previous studies demonstrate mHtt SUMOylation, a process of covalent attachment of small ubiquitin-like modifiers (SUMO) to target proteins. Protein polySUMOylation further triggers its ubiquitination and segregation by the polySUMO axis. Here, we examined how SUMOylation regulates aggregation and degradation of Htt103QP-GFP, a model mHtt, in budding yeast. We first confirmed Htt103QP-GFP SUMOylation in budding yeast. We also found that recruitment of the SUMO E2-conjugating enzyme to Htt103QP-GFP accelerates its aggregation, but recruitment of a SUMO protease to Htt103QP-GFP delays this process. Disruption of the polySUMO axis led to increased Htt103QP-GFP aggregation. Interestingly, the results from fluorescence recovery after photobleaching assay and treatment with a biomolecular condensate-disrupting chemical indicate that SUMOylation accelerates biomolecular condensate formation of Htt103QP-GFP. Importantly, impaired SUMOylation delays Htt103QP-GFP proteasomal degradation and accelerates formation of SDS-insoluble Htt103QP-GFP aggregates. Together, these results indicate that SUMOylation facilitates proteasomal degradation of misfolded proteins by retaining their solubility.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar77"},"PeriodicalIF":3.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004222","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