Molecular Biology of the Cell最新文献

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":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dimerization activates the Inversin complex in C. elegans. 二聚化激活了秀丽隐杆线虫中的 Inversin 复合物。

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.E24-05-0218

Erika Beyrent, Derek T Wei, Gwendolyn M Beacham, Sangwoo Park, Jian Zheng, Matthew J Paszek, Gunther Hollopeter

{"title":"Dimerization activates the Inversin complex in C. elegans.","authors":"Erika Beyrent, Derek T Wei, Gwendolyn M Beacham, Sangwoo Park, Jian Zheng, Matthew J Paszek, Gunther Hollopeter","doi":"10.1091/mbc.E24-05-0218","DOIUrl":"10.1091/mbc.E24-05-0218","url":null,"abstract":"Genetic, colocalization, and biochemical studies suggest that the ankyrin repeat-containing proteins Inversin (INVS) and ANKS6 function with the NEK8 kinase to control tissue patterning and maintain organ physiology. It is unknown whether these three proteins assemble into a static \"Inversin complex\" or one that adopts multiple bioactive forms. Through the characterization of hyperactive alleles in C. elegans, we discovered that the Inversin complex is activated by dimerization. Genome engineering of an RFP tag onto the nematode homologues of INVS (MLT-4) and NEK8 (NEKL-2) induced a gain-of-function, cyst-like phenotype that was suppressed by monomerization of the fluorescent tag. Stimulated dimerization of MLT-4 or NEKL-2 using optogenetics was sufficient to recapitulate the phenotype of a constitutively active Inversin complex. Further, dimerization of NEKL-2 bypassed a lethal MLT-4 mutant, demonstrating that the dimeric form is required for function. We propose that dynamic switching between at least two functionally distinct states - an active dimer and an inactive monomer - gates the output of the Inversin complex.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902364","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

Calcineurin promotes adaptation to chronic stress through two distinct mechanisms. 钙调素通过两种不同的机制促进对慢性压力的适应。

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.E24-03-0122

Mackenzie J Flynn, Nicholas W Harper, Rui Li, Lihua Julie Zhu, Michael J Lee, Jennifer A Benanti

{"title":"Calcineurin promotes adaptation to chronic stress through two distinct mechanisms.","authors":"Mackenzie J Flynn, Nicholas W Harper, Rui Li, Lihua Julie Zhu, Michael J Lee, Jennifer A Benanti","doi":"10.1091/mbc.E24-03-0122","DOIUrl":"10.1091/mbc.E24-03-0122","url":null,"abstract":"Adaptation to environmental stress requires coordination between stress-defense programs and cell cycle progression. The immediate response to many stressors has been well characterized, but how cells survive in challenging environments long term is unknown. Here, we investigate the role of the stress-activated phosphatase calcineurin (CN) in adaptation to chronic CaCl2 stress in Saccharomyces cerevisiae. We find that prolonged exposure to CaCl2 impairs mitochondrial function and demonstrate that cells respond to this stressor using two CN-dependent mechanisms-one that requires the downstream transcription factor Crz1 and another that is Crz1 independent. Our data indicate that CN maintains cellular fitness by promoting cell cycle progression and preventing CaCl2-induced cell death. When Crz1 is present, transient CN activation suppresses cell death and promotes adaptation despite high levels of mitochondrial loss. However, in the absence of Crz1, prolonged activation of CN prevents mitochondrial loss and further cell death by upregulating glutathione biosynthesis genes thereby mitigating damage from reactive oxygen species. These findings illustrate how cells maintain long-term fitness during chronic stress and suggest that CN promotes adaptation in challenging environments by multiple mechanisms.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860283","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 single septin from a polyextremotolerant yeast recapitulates many canonical functions of septin hetero-oligomers. 一种来自多极端耐受性酵母的单一septin重现了septin异质配体的许多典型功能。

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.E24-05-0227

Grace E Hamilton, Katherine N Wadkovsky, Amy S Gladfelter

{"title":"A single septin from a polyextremotolerant yeast recapitulates many canonical functions of septin hetero-oligomers.","authors":"Grace E Hamilton, Katherine N Wadkovsky, Amy S Gladfelter","doi":"10.1091/mbc.E24-05-0227","DOIUrl":"10.1091/mbc.E24-05-0227","url":null,"abstract":"Morphological complexity and plasticity are hallmarks of polyextremotolerant fungi. Septins are conserved cytoskeletal proteins and key contributors to cell polarity and morphogenesis. They sense membrane curvature, coordinate cell division, and influence diffusion at the plasma membrane. Four septin homologues are conserved from yeasts to humans, the systems in which septins have been most studied. But there is also a fifth family of opisthokont septins that remain biochemically mysterious. Members of this family, Group 5 septins, appear in the genomes of filamentous fungi, but are understudied due to their absence from ascomycete yeasts. Knufia petricola is an emerging model polyextremotolerant black fungus that can also serve as a model system for Group 5 septins. We have recombinantly expressed and biochemically characterized KpAspE, a Group 5 septin from K. petricola. This septin--by itself in vitro--recapitulates many functions of canonical septin hetero-octamers. KpAspE is an active GTPase that forms diverse homo-oligomers, binds shallow membrane curvatures, and interacts with the terminal subunit of canonical septin hetero-octamers. These findings raise the possibility that Group 5 septins govern the higher-order structures formed by canonical septins, which in K. petricola cells form extended filaments, and provide insight into how septin hetero-oligomers evolved from ancient homomers.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142086178","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