Molecular Biology of the Cell最新文献_第8页

Med13 is required for efficient P-body recruitment and autophagic degradation of Edc3 following nitrogen starvation. 氮饥饿后，Edc3 的高效 P 体招募和自噬降解需要 Med13。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-11-01 Epub Date: 2024-09-25 DOI: 10.1091/mbc.E23-12-0470

Sara E Hanley, Stephen D Willis, Brittany Friedson, Katrina F Cooper

{"title":"Med13 is required for efficient P-body recruitment and autophagic degradation of Edc3 following nitrogen starvation.","authors":"Sara E Hanley, Stephen D Willis, Brittany Friedson, Katrina F Cooper","doi":"10.1091/mbc.E23-12-0470","DOIUrl":"10.1091/mbc.E23-12-0470","url":null,"abstract":"The Cdk8 kinase module (CKM), a conserved, detachable unit of the Mediator complex, plays a vital role in regulating transcription and communicating stress signals from the nucleus to other organelles. Here, we describe a new transcription-independent role for Med13, a CKM scaffold protein, following nitrogen starvation. In Saccharomyces cerevisiae, nitrogen starvation triggers Med13 to translocate to the cytoplasm. This stress also induces the assembly of conserved membraneless condensates called processing bodies (P-bodies) that dynamically sequester translationally inactive messenger ribonucleoprotein particles. Cytosolic Med13 colocalizes with P-bodies, where it helps recruit Edc3, a highly conserved decapping activator and P-body assembly factor, into these conserved ribonucleoprotein granules. Moreover, Med13 orchestrates the autophagic degradation of Edc3 through a selective cargo-hitchhiking autophagy pathway that utilizes Ksp1 as its autophagic receptor protein. In contrast, the autophagic degradation of Xrn1, another conserved P-body assembly factor, is Med13 independent. These results place Med13 as a new player in P-body assembly and regulation following nitrogen starvation. They support a model in which Med13 acts as a conduit between P-bodies and phagophores, two condensates that use liquid-liquid phase separation in their assembly.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar142"},"PeriodicalIF":3.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350261","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

Nuclear basket proteins regulate the distribution and mobility of nuclear pore complexes in budding yeast. 核篮蛋白调节芽殖酵母中核孔复合体的分布和流动性。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-11-01 Epub Date: 2024-09-25 DOI: 10.1091/mbc.E24-08-0371

Janka Zsok, Francois Simon, Göksu Bayrak, Luljeta Isaki, Nina Kerff, Yoana Kicheva, Amy Wolstenholme, Lucien E Weiss, Elisa Dultz

{"title":"Nuclear basket proteins regulate the distribution and mobility of nuclear pore complexes in budding yeast.","authors":"Janka Zsok, Francois Simon, Göksu Bayrak, Luljeta Isaki, Nina Kerff, Yoana Kicheva, Amy Wolstenholme, Lucien E Weiss, Elisa Dultz","doi":"10.1091/mbc.E24-08-0371","DOIUrl":"10.1091/mbc.E24-08-0371","url":null,"abstract":"Nuclear pore complexes (NPCs) mediate all traffic between the nucleus and the cytoplasm and are among the most stable protein assemblies in cells. Budding yeast cells carry two variants of NPCs which differ in the presence or absence of the nuclear basket proteins Mlp1, Mlp2, and Pml39. The binding of these basket proteins occurs very late in NPC assembly and Mlp-positive NPCs are excluded from the region of the nuclear envelope that borders the nucleolus. Here, we use recombination-induced tag exchange to investigate the stability of all the NPC subcomplexes within individual NPCs. We show that the nuclear basket proteins Mlp1, Mlp2, and Pml39 remain stably associated with NPCs through multiple cell-division cycles, and that Mlp1/2 are responsible for the exclusion of NPCs from the nucleolar territory. In addition, we demonstrate that binding of the FG-nucleoporins Nup1 and Nup2 depletes also Mlp-negative NPCs from this region by an independent pathway. We develop a method for single NPC tracking in budding yeast and observe that NPCs exhibit increased mobility in the absence of nuclear basket components. Our data suggest that the distribution of NPCs on the nucleus is governed by multiple interaction of nuclear basket proteins with the nuclear interior.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar143"},"PeriodicalIF":3.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350262","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

G3BP isoforms differentially affect stress granule assembly and gene expression during cellular stress. 在细胞应激过程中，G3BP 同工酶会对应激颗粒的组装和基因表达产生不同影响。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-11-01 Epub Date: 2024-10-02 DOI: 10.1091/mbc.E24-02-0062

José M Liboy-Lugo, Carla A Espinoza, Jessica Sheu-Gruttadauria, Jesslyn E Park, Albert Xu, Ziad Jowhar, Angela L Gao, José A Carmona-Negrón, Torsten Wittmann, Natalia Jura, Stephen N Floor

{"title":"G3BP isoforms differentially affect stress granule assembly and gene expression during cellular stress.","authors":"José M Liboy-Lugo, Carla A Espinoza, Jessica Sheu-Gruttadauria, Jesslyn E Park, Albert Xu, Ziad Jowhar, Angela L Gao, José A Carmona-Negrón, Torsten Wittmann, Natalia Jura, Stephen N Floor","doi":"10.1091/mbc.E24-02-0062","DOIUrl":"10.1091/mbc.E24-02-0062","url":null,"abstract":"Stress granules (SGs) are macromolecular assemblies that form under cellular stress. Formation of these membraneless organelles is driven by the condensation of RNA and RNA-binding proteins such as G3BPs. G3BPs form SGs following stress-induced translational arrest. Three G3BP paralogues (G3BP1, G3BP2A, and G3BP2B) have been identified in vertebrates. However, the contribution of different G3BP paralogues to SG formation and gene expression changes is incompletely understood. Here, we probed the functions of G3BPs by identifying important residues for SG assembly at their N-terminal domain such as V11. This conserved amino acid is required for formation of the G3BP-Caprin-1 complex, hence promoting SG assembly. Total RNA sequencing and ribosome profiling revealed that a G3BPV11A mutant leads to changes in mRNA levels and ribosome engagement during the integrated stress response (ISR). Moreover, we found that G3BP2B preferentially forms SGs and promotes changes in mRNA expression under endoplasmic reticulum (ER) stress. Furthermore, our work is a resource for researchers to study gene expression changes under cellular stress. Together, this work suggests that perturbing protein-protein interactions mediated by G3BPs affect SG assembly and gene expression during the ISR, and such functions are differentially regulated by G3BP paralogues under ER stress.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar140"},"PeriodicalIF":3.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365798","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

The RhoGEF protein Plekhg5 self-associates via its PH domain to regulate apical cell constriction. RhoGEF蛋白Plekhg5通过其PH结构域自我结合，调节顶端细胞收缩。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-10-01 Epub Date: 2024-08-28 DOI: 10.1091/mbc.E24-04-0179

Ivan K Popov, Jiahui Tao, Chenbei Chang

{"title":"The RhoGEF protein Plekhg5 self-associates via its PH domain to regulate apical cell constriction.","authors":"Ivan K Popov, Jiahui Tao, Chenbei Chang","doi":"10.1091/mbc.E24-04-0179","DOIUrl":"10.1091/mbc.E24-04-0179","url":null,"abstract":"RhoGEFs are critical activators of Rho family small GTPases and regulate diverse biological processes, such as cell division and tissue morphogenesis. We reported previously that the RhoGEF gene plekhg5 controls apical constriction of bottle cells at the blastopore lip during Xenopus gastrulation, but the detailed mechanism of plekhg5 action is not understood in depth. In this study, we show that localization of Plekhg5 in the apical cortex depends on its N-terminal sequences and intact guanine nucleotide exchange activity, whereas the C-terminal sequences prevent ectopic localization of the protein to the basolateral compartment. We also reveal that Plekhg5 self-associates via its PH domain, and this interaction leads to functional rescue of two mutants that lack the N-terminal region and the guanine nucleotide exchange factor activity, respectively, in trans. A point mutation in the PH domain corresponding to a variant associated with human disease leads to loss of self-association and failure of the mutant to induce apical constriction. Taken together, our results suggest that PH-mediated self-association and N-terminal domain-mediated subcellular localization are both crucial for the function of Plekhg5 in inducing apical constriction.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar134"},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142086180","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

P4-ATPase endosomal recycling relies on multiple retromer-dependent localization signals. P4-ATP 酶的内体再循环依赖于多种 retromer 依赖性定位信号。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-10-01 Epub Date: 2024-08-07 DOI: 10.1091/mbc.E24-05-0209

Mariana Jiménez, Claire K Kyoung, Kateryna Nabukhotna, Davia Watkins, Bhawik K Jain, Jordan T Best, Todd R Graham

引用次数: 0

Yellow and oxidation-resistant derivatives of a monomeric superfolder GFP. 单体超级文件夹 GFP 的黄色和抗氧化衍生物。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-10-01 Epub Date: 2024-08-14 DOI: 10.1091/mbc.E24-01-0035

Fernando M Valbuena, Adam H Krahn, Sherzod A Tokamov, Annie C Greene, Richard G Fehon, Benjamin S Glick

引用次数: 0

Inhibition of Mac-1 allows human macrophages to migrate against the direction of shear flow on ICAM-1. 抑制 Mac-1 可使人类巨噬细胞逆 ICAM-1 的剪切流方向迁移。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-10-01 Epub Date: 2024-08-21 DOI: 10.1091/mbc.E24-03-0114

Aman Mittal, Subham Guin, Ai Mochida, Daniel A Hammer, Alexander Buffone

{"title":"Inhibition of Mac-1 allows human macrophages to migrate against the direction of shear flow on ICAM-1.","authors":"Aman Mittal, Subham Guin, Ai Mochida, Daniel A Hammer, Alexander Buffone","doi":"10.1091/mbc.E24-03-0114","DOIUrl":"10.1091/mbc.E24-03-0114","url":null,"abstract":"All immune cells must transit from the blood to distal sites such as the lymph nodes, bone marrow, or sites of infection. Blood borne monocytes traffic to the site of inflammation by adhering to the endothelial surface and migrating along endothelial intracellular adhesion molecule 1 (ICAM-1) by their ligand's macrophage 1 antigen (Mac-1) and lymphocyte functional antigen 1 (LFA-1) to transmigrate through the endothelium. Poor patient prognoses in chronic inflammation and tumors have been attributed to the hyper recruitment of certain types of macrophages. Therefore, targeting the binding of ICAM-1 to its respective ligands provides a novel approach to targeting the recruitment of macrophages. To that end, we determined whether the loss of Mac-1 expression could induce this upstream migration behavior by using blocking antibodies against Mac-1 to examine the effects of hydrodynamic flow on the migration of the human macrophage cell line U-937 on ICAM-1 surfaces. Blocking Mac-1 on U-937 cells led to upstream migration against the direction of shear flow on ICAM-1 surfaces. In sum, the ability of macrophages to migrate upstream when Mac-1 is blocked represents a new avenue to precisely control the differentiation, migration, and trafficking of macrophages.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"br18"},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017994","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

Proviral role of ATG2 autophagy related protein in tomato bushy stunt virus replication through bulk phospholipid transfer into the viral replication organelle. ATG2 自噬相关蛋白通过将大量磷脂转移到病毒复制细胞器中，在番茄矮花叶病毒复制过程中发挥了病毒载体的作用。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-10-01 Epub Date: 2024-08-07 DOI: 10.1091/mbc.E24-05-0236

Yuanrong Kang, Judit Pogany, Peter D Nagy

{"title":"Proviral role of ATG2 autophagy related protein in tomato bushy stunt virus replication through bulk phospholipid transfer into the viral replication organelle.","authors":"Yuanrong Kang, Judit Pogany, Peter D Nagy","doi":"10.1091/mbc.E24-05-0236","DOIUrl":"10.1091/mbc.E24-05-0236","url":null,"abstract":"Subversion of cellular membranes and membrane proliferation are used by positive-strand RNA viruses to build viral replication organelles (VROs) that support virus replication. The biogenesis of the membranous VROs requires major changes in lipid metabolism and lipid transfer in infected cells. In this work, we show that tomato bushy stunt virus (TBSV) hijacks Atg2 autophagy related protein with bulk lipid transfer activity into VROs via interaction with TBSV p33 replication protein. Deletion of Atg2 in yeast and knockdown of Atg2 in Nicotiana benthamiana resulted in decreased TBSV replication. We found that subversion of Atg2 by TBSV was important to enrich VRO membranes with phosphatidylethanolamine (PE), phosphatidylserine (PS) and PI(3)P phosphoinositide. Interestingly, inhibition of autophagy did not affect the efficient recruitment of Atg2 into VROs, and overexpression of Atg2 enhanced TBSV replication, indicating autophagy-independent subversion of Atg2 by TBSV. These findings suggest that the proviral function of Atg2 lipid transfer protein is in VRO membrane proliferation. In addition, we find that Atg2 interacting partner Atg9 with membrane lipid-scramblase activity is also coopted for tombusvirus replication. Altogether, the subversion of Atg2 bridge-type lipid transfer protein provides a new mechanism for tombusviruses to greatly expand VRO membranes to support robust viral replication.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar124"},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902366","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

Complex state transitions of the bacterial cell division protein FtsZ. 细菌细胞分裂蛋白 FtsZ 的复杂状态转换。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-10-01 Epub Date: 2024-07-31 DOI: 10.1091/mbc.E23-11-0446

Benjamin D Knapp, Handuo Shi, Kerwyn Casey Huang

{"title":"Complex state transitions of the bacterial cell division protein FtsZ.","authors":"Benjamin D Knapp, Handuo Shi, Kerwyn Casey Huang","doi":"10.1091/mbc.E23-11-0446","DOIUrl":"10.1091/mbc.E23-11-0446","url":null,"abstract":"The key bacterial cell division protein FtsZ can adopt multiple conformations, and prevailing models suggest that transitions of FtsZ subunits from the closed to open state are necessary for filament formation and stability. Using all-atom molecular dynamics simulations, we analyzed state transitions of Staphylococcus aureus FtsZ as a monomer, dimer, and hexamer. We found that monomers can adopt intermediate states but preferentially adopt a closed state that is robust to forced reopening. Dimer subunits transitioned between open and closed states, and dimers with both subunits in the closed state remained highly stable, suggesting that open-state conformations are not necessary for filament formation. Mg2+ strongly stabilized the conformation of GTP-bound subunits and the dimer filament interface. Our hexamer simulations indicate that the plus end subunit preferentially closes and that other subunits can transition between states without affecting inter-subunit stability. We found that rather than being correlated with subunit opening, inter-subunit stability was strongly correlated with catalytic site interactions. By leveraging deep-learning models, we identified key intrasubunit interactions governing state transitions. Our findings suggest a greater range of possible monomer and filament states than previously considered and offer new insights into the nuanced interplay between subunit states and the critical role of nucleotide hydrolysis and Mg2+ in FtsZ filament dynamics.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar130"},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860284","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

The CCT chaperonin and actin modulate the ER and RNA-binding protein condensation during oogenesis and maintain translational repression of maternal mRNA and oocyte quality. 在卵子发生过程中，CCT伴侣蛋白和肌动蛋白调节ER和RNA结合蛋白的凝聚，维持母体mRNA的翻译抑制和卵母细胞的质量。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-10-01 Epub Date: 2024-08-21 DOI: 10.1091/mbc.E24-05-0216

Mohamed T Elaswad, Mingze Gao, Victoria E Tice, Cora G Bright, Grace M Thomas, Chloe Munderloh, Nicholas J Trombley, Christya N Haddad, Ulysses G Johnson, Ashley N Cichon, Jennifer A Schisa

{"title":"The CCT chaperonin and actin modulate the ER and RNA-binding protein condensation during oogenesis and maintain translational repression of maternal mRNA and oocyte quality.","authors":"Mohamed T Elaswad, Mingze Gao, Victoria E Tice, Cora G Bright, Grace M Thomas, Chloe Munderloh, Nicholas J Trombley, Christya N Haddad, Ulysses G Johnson, Ashley N Cichon, Jennifer A Schisa","doi":"10.1091/mbc.E24-05-0216","DOIUrl":"10.1091/mbc.E24-05-0216","url":null,"abstract":"The regulation of maternal mRNAs is essential for proper oogenesis, the production of viable gametes, and to avoid birth defects and infertility. Many oogenic RNA-binding proteins have been identified with roles in mRNA metabolism, some of which localize to dynamic ribonucleoprotein granules and others that appear dispersed. Here, we use a combination of in vitro condensation assays and the in vivo Caenorhabditis elegans oogenesis model to characterize the properties of the conserved KH-domain MEX-3 protein and to identify novel regulators of MEX-3 and three other translational regulators. We demonstrate that MEX-3 undergoes phase separation and appears to have intrinsic gel-like properties in vitro. We also identify novel roles for the chaperonin-containing tailless complex polypeptide 1 (CCT) chaperonin and actin in preventing ectopic RNA-binding protein condensates in maturing oocytes that appear to be independent of MEX-3 folding. The CCT chaperonin and actin also oppose the expansion of endoplasmic reticulum sheets that may promote ectopic condensation of RNA-binding proteins. These novel regulators of condensation are also required for the translational repression of maternal mRNA which is essential for oocyte quality and fertility. The identification of this regulatory network may also have implications for understanding the role of hMex3 phase transitions in cancer.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar131"},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017995","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