Molecular Biology of the Cell最新文献

Tubulin acetylation deficiency promotes axonemal turnover and increases cytoplasmic microtubules. 微管蛋白乙酰化缺乏促进轴突更新和增加细胞质微管。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2026-06-01 Epub Date: 2026-04-15 DOI: 10.1091/mbc.E26-01-0058

Tomohiro Kubo, Natsumi Tajima-Shirasaki, Rinka Sasaki, Toshiyuki Oda, Masayuki Onishi

{"title":"Tubulin acetylation deficiency promotes axonemal turnover and increases cytoplasmic microtubules.","authors":"Tomohiro Kubo, Natsumi Tajima-Shirasaki, Rinka Sasaki, Toshiyuki Oda, Masayuki Onishi","doi":"10.1091/mbc.E26-01-0058","DOIUrl":"10.1091/mbc.E26-01-0058","url":null,"abstract":"Tubulin post-translational modifications regulate microtubule dynamics. Although α-tubulin acetylation has been linked to microtubule stability, how this modification affects the overall organization of cellular microtubules remains obscure. Here, we generated a Chlamydomonas mutant lacking the acetyltransferase αTAT1, which completely abolished α-tubulin K40 acetylation. Surprisingly, the steady-state lengths of normally acetylated structures, axonemes, and rootlets were largely unaffected. αTAT1 was found to localize to the ciliary tip, where it may stabilize the distal axoneme. Consistent with this, loss of acetylation caused an increase in axonemal tubulin turnover, as revealed by dikaryon-fusion assays. Unexpectedly, the atat1-1 mutant displayed an increased number of dynamic cortical microtubules and could regenerate long cilia after amputation, even when protein synthesis was inhibited. Notably, this increase in cortical microtubules required the presence of cilia, as the atat1-1 mutant carrying the ift46-1 mutation, which abolishes ciliogenesis, exhibited normal cortical microtubule levels. Despite these dramatic cytoskeletal changes, cell growth and division remained essentially normal. These findings suggest that acetylation modulates microtubule behavior by regulating axonemal tubulin turnover and cytoplasmic microtubule dynamics, while cellular morphology is buffered against variations in microtubule content.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar48"},"PeriodicalIF":2.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691195","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

Endothelial β-PIX (ARHGEF7) supports actomyosin mediated expulsion of VWF through dynamic reorganization of the cytoskeleton. 内皮细胞β-PIX （ARHGEF7）通过细胞骨架的动态重组支持肌动球蛋白介导的VWF的排出。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2026-06-01 Epub Date: 2026-05-04 DOI: 10.1091/mbc.E25-10-0483

Sammy El-Mansi, Karishma M Deegan, Thomas D Nightingale

{"title":"Endothelial β-PIX (ARHGEF7) supports actomyosin mediated expulsion of VWF through dynamic reorganization of the cytoskeleton.","authors":"Sammy El-Mansi, Karishma M Deegan, Thomas D Nightingale","doi":"10.1091/mbc.E25-10-0483","DOIUrl":"10.1091/mbc.E25-10-0483","url":null,"abstract":"Endothelial cells promote thrombosis and hemostasis through the secretion of von Willebrand Factor (VWF) from their secretory granules-the Weibel-Palade bodies (WPBs). In response to specific stimuli, dynamic actin nucleation and remodeling of the cytoskeleton facilitates the expulsion of ultra-large VWF multimers to elevate plasma VWF and to form a platform for platelet capture and thrombus formation. P21 activated kinase 2 (PAK2) is a crucial regulator of the actin cytoskeleton and is essential for VWF secretion in response to secretagogues which utilize actomyosin mediated exocytosis. Here, we characterize the role of β-PAK-interacting exchange factor (β-PIX) in WPB exocytosis. Inhibition of β-PIX function prevents dynamic cytoskeletal remodeling resulting in reduced VWF secretion. Depletion of β-PIX using siRNA reduced the number of WPB fusion events, prolonged the time taken for GFP-VWF to be secreted post-fusion and delayed kinetics of the exocytic actomyosin ring. Use of full length and truncated β-PIX demonstrated that the PAK interacting and GEF domain mediate cytoskeletal remodeling whereas only the full-length construct could rescue VWF secretion. β-PIX regulates both septin ring formation and cofilin mediated actin remodeling during actomyosin ring function. These data identify β-PIX as a regulator of endothelial exocytosis through supporting actomyosin-mediated expulsion of VWF.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar49"},"PeriodicalIF":2.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776223","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

YeastSAM: A deep learning model for accurate segmentation of yeast cells. 酵母细胞精确分割的深度学习模型。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2026-06-01 Epub Date: 2026-05-08 DOI: 10.1091/mbc.E25-09-0454

Yonghao Zhao, Zhouyuan Zhu, Sen Yang, Weihan Li

引用次数: 0

Septins associate with AP-3 to support trafficking to the vacuole/lysosome in yeast. septin与AP-3相关，以支持酵母液泡/溶酶体的运输。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2026-06-01 Epub Date: 2026-04-15 DOI: 10.1091/mbc.E26-01-0055

Mitchell Leih, Michaela McCright, Cortney Angers, Michael Davey, Elizabeth Conibear, Alex Merz, Greg Odorizzi

{"title":"Septins associate with AP-3 to support trafficking to the vacuole/lysosome in yeast.","authors":"Mitchell Leih, Michaela McCright, Cortney Angers, Michael Davey, Elizabeth Conibear, Alex Merz, Greg Odorizzi","doi":"10.1091/mbc.E26-01-0055","DOIUrl":"10.1091/mbc.E26-01-0055","url":null,"abstract":"Adaptor protein complex 3 (AP-3) mediates clathrin-independent transport to lysosomes, yet accessory factors supporting this pathway remain incompletely defined. In Saccharomyces cerevisiae, the C-terminal intrinsically disordered regions (IDRs) of both AP-3 large subunits (δ and β3) serve as platforms for association with accessory factors. Through proteomic analysis of proteins associated with these IDRs, we identify the septin cytoskeleton as a candidate AP-3-associated factor. Bimolecular fluorescence complementation (BiFC) reveals a hierarchical pattern of association: AP-3 shows preferential proximity to core septin subunits (Cdc10, Cdc3, and Cdc12) over terminal subunits (Cdc11 and Shs1). These terminal subunits serve as alternative caps of septin octamers, generating structurally distinct assemblies. Significantly, dysfunction of Cdc11 but not Shs1 selectively impairs AP-3-dependent cargo sorting without affecting the parallel vacuolar protein sorting (VPS) pathway to the vacuole (lysosome in yeast), providing genetic evidence for a specific functional connection between Cdc11-containing septin assemblies and AP-3-mediated transport.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"br19"},"PeriodicalIF":2.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691136","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

Cytokinetic abscission failures in a polarized epithelium affect apical membrane size and cilia. 极化上皮细胞动力学脱落失败影响尖膜大小和纤毛。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2026-06-01 Epub Date: 2026-04-08 DOI: 10.1091/mbc.E25-09-0444

Kaela S Lettieri, Katrina C McNeely, Noelle D Dwyer

{"title":"Cytokinetic abscission failures in a polarized epithelium affect apical membrane size and cilia.","authors":"Kaela S Lettieri, Katrina C McNeely, Noelle D Dwyer","doi":"10.1091/mbc.E25-09-0444","DOIUrl":"10.1091/mbc.E25-09-0444","url":null,"abstract":"Cytokinetic abscission genes are linked to cancers and developmental disorders, but the consequences of disrupted abscission in vivo remain under-explored. Previously we showed that in the forebrain of Cep55 knockout (KO) mouse embryos, a subset of neuroepithelial stem cells (NSCs) fail abscission and become binucleate, and some of those undergo p53-mediated apoptosis. Here we use the Cep55 KO to investigate how stochastic abscission failures in a polarized epithelium affect the epithelial architecture. We find that NSCs in Cep55 KO neuroepithelium have preserved epithelial polarity and integrity. However, they have enlarged apical membranes (called apical endfeet), longer primary cilia, and increased biciliation. We then test whether the enlarged apical endfeet arise from filling the space of apoptotic neighbors. Remarkably, blocking apoptosis does not rescue but exacerbates the phenotypes: extra-large apical endfeet have further increased multiciliation, supernumerary centrosomes, and abnormal or multiple nuclei, although epithelial polarity is maintained. These findings elucidate the importance of proper abscission in maintaining polarized epithelial structure, and reveal that p53-mediated apoptosis is a crucial guardian of tissue architecture when cell division defects arise during development and disease.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar47"},"PeriodicalIF":2.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13086364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633822","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

Asymmetric branched F-actin networks at apical clathrin coated pits support microvillar biogenesis. 不对称分支的f -肌动蛋白网络支持微绒毛的生物发生。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2026-06-01 Epub Date: 2026-04-08 DOI: 10.1091/mbc.E25-12-0606

Olivia L Perkins, Malcom Díaz García, Matthew J Tyska

{"title":"Asymmetric branched F-actin networks at apical clathrin coated pits support microvillar biogenesis.","authors":"Olivia L Perkins, Malcom Díaz García, Matthew J Tyska","doi":"10.1091/mbc.E25-12-0606","DOIUrl":"10.1091/mbc.E25-12-0606","url":null,"abstract":"Microvilli are conserved actin-based protrusions that expand surface area and absorptive capacity in epithelial tissues. In humans, the intestinal tract grows 300 trillion microvilli per day, yet the molecular mechanisms defining where and when microvilli grow remain unclear. Using a combination of live-cell confocal and super-resolution microscopy to investigate native intestinal tissues and epithelial cell culture models, we found that microvilli grow from Arp2/3-generated branched actin networks that form on the surface of clathrin-coated pits. These transient networks are stabilized by cortactin and localize to the apical plasma membrane minutes before reorganizing into the linear core actin bundles that support microvilli. Moreover, subpixel precision localization of coated pit and microvilli markers revealed that F-actin asymmetrically localizes to one side of a nascent clathrin-coated pit, and that microvilli grow from the side with the highest F-actin density. These findings support a model where the asymmetric accumulation of F-actin and growing barbed ends on the surface of a clathrin-coated pit offers a filament source to support microvilli formation.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"br18"},"PeriodicalIF":2.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633845","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 MAP kinase cascade modulates expression of late G1 phase cyclins in budding yeast. MAP激酶级联调节出芽酵母G1期晚期细胞周期蛋白的表达。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2026-06-01 Epub Date: 2026-04-15 DOI: 10.1091/mbc.E25-12-0575

Navid Zebarjadi, Douglas R Kellogg

{"title":"A MAP kinase cascade modulates expression of late G1 phase cyclins in budding yeast.","authors":"Navid Zebarjadi, Douglas R Kellogg","doi":"10.1091/mbc.E25-12-0575","DOIUrl":"10.1091/mbc.E25-12-0575","url":null,"abstract":"Expression of late G1 phase cyclins is the critical molecular event that marks commitment to enter the cell cycle. In budding yeast, late G1 phase cyclins initiate and sustain the growth of a new daughter bud, so their expression also marks the start of a new growth phase during the cell cycle. Expression of late G1 phase cyclins is influenced by nutrient availability-cells growing in poor nutrients progress through the late G1 phase with lower levels of late G1 phase cyclins. However, little is known about how or why nutrients modulate expression of late G1 phase cyclins. Here, we investigated the signals that control expression of the late G1 phase cyclin Cln2. We discovered that nutrients modulate the expression of Cln2 via post-transcriptional mechanisms that influence Cln2 phosphorylation and turnover. Nutrient modulation of Cln2 protein expression requires a TORC2-MAP kinase signaling axis. Expression of Cln2 is closely correlated with bud growth and is required for bud growth. A model that could explain the data is that nutrients modulate Cln2 expression to ensure that the rate of bud growth is matched to the availability of nutrients that support bud growth.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar51"},"PeriodicalIF":2.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691146","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

Ligase-dependent and independent functions of the C-terminus of Mms21 contribute to optimal growth and genome stability in Saccharomyces cerevisiae. Mms21的连接酶依赖性和c端独立功能有助于酿酒酵母的最佳生长和基因组稳定性。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2026-06-01 Epub Date: 2026-04-08 DOI: 10.1091/mbc.E25-11-0567

Cheung Li, Anny Vo, Nkechinye Baadi, Yee Mon Thu

{"title":"Ligase-dependent and independent functions of the C-terminus of Mms21 contribute to optimal growth and genome stability in Saccharomyces cerevisiae.","authors":"Cheung Li, Anny Vo, Nkechinye Baadi, Yee Mon Thu","doi":"10.1091/mbc.E25-11-0567","DOIUrl":"10.1091/mbc.E25-11-0567","url":null,"abstract":"An evolutionarily conserved E3 SUMO ligase, Mms21, orchestrates genome integrity processes. Our study examined a mutant of Saccharomyces cerevisiae Mms21, analogous to a mutant identified in a rare human condition characterized by genome instability. The human mutation C-terminally truncated the Mms21 protein, without affecting the residues in the E3 ligase domain. Thus, we hypothesized that the C-terminus regulated ligase-independent functions of Mms21. Truncating the last 22 amino acids of yeast Mms21-designated as mms21Δ22 mutants-mimicked the human disease mutation. mms21Δ22 mutants exhibited slower growth and increased DNA damage sensitivity than the wild-type and two well-characterized mutants of Mms21-one with two missense mutations in the enzymatic domain and another without the entire enzymatic domain and the C-terminus. Furthermore, mms21Δ22 mutants exhibited a G2-M delay during unchallenged growth. The mms21Δ22 allele reduced Mms21 protein levels, but the phenotypes of mms21Δ22 mutants simply could not be attributed to diminished protein levels. Our genetic data suggested that the C-terminus contributed to both ligase-dependent and -independent functions of Mms21 and opposed the activity of the adjacent domain, thereby fine-tuning genome integrity. The mms21Δ22 disease allele analogue further enhanced our understanding of Mms21's functions beyond its ligase activity in genome instability conditions.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar50"},"PeriodicalIF":2.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633804","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

Polarized anionic phospholipids and exocytosis are implicated in the polarized recruitment of budding yeast AP180, an endocytic initiator. 极化阴离子磷脂和胞吐作用与芽殖酵母AP180（一种内吞引发剂）的极化招募有关。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2026-06-01 Epub Date: 2026-04-08 DOI: 10.1091/mbc.E24-10-0446

Paul Marchando, Gean Hu, Feng Yuan, Jordan M Ngo, Yidi Sun, David G Drubin

引用次数: 0

Matrix stiffness and stress relaxation regulate osteogenesis through histone demethylases KDM4B and KDM6B. 基质刚度和应力松弛通过组蛋白去甲基化酶KDM4B和KDM6B调节成骨。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2026-05-01 Epub Date: 2026-03-11 DOI: 10.1091/mbc.E25-07-0331

Ian M Tayler, Amy Zhu, Abhishek Sharma, Neha Saxena, Siddharth S Dey, Ryan S Stowers

{"title":"Matrix stiffness and stress relaxation regulate osteogenesis through histone demethylases KDM4B and KDM6B.","authors":"Ian M Tayler, Amy Zhu, Abhishek Sharma, Neha Saxena, Siddharth S Dey, Ryan S Stowers","doi":"10.1091/mbc.E25-07-0331","DOIUrl":"10.1091/mbc.E25-07-0331","url":null,"abstract":"Stem cells sense biophysical cues within their extracellular microenvironment and respond via mechanotransduction signaling pathways that induce changes in gene expression and associated cell fate outcomes. Histone-modifying enzymes are known to drive stem cell differentiation through changes in chromatin accessibility, but little is understood as to how extracellular matrix (ECM) mechanics regulate epigenomic remodeling. Here, we utilized alginate hydrogels with tunable mechanical properties to investigate the role of both matrix stiffness and stress relaxation on histone demethylase expression and activity during osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). Our results revealed that the expression of two histone demethylases, KDM4B and KDM6B, was upregulated during osteogenesis in response to stiff and fast stress-relaxing matrix conditions. Additionally, CUT&Tag profiling coupled with RNA-sequencing demonstrated that repressive histone methylation was decreased at osteogenic-specific loci in stiff, fast-relaxing matrices. Further, inhibition of mechanotransduction signaling pathways reduced expression of KDM4B and KDM6B and hindered osteogenic differentiation overall. Interestingly, phosphorylation of SMAD 1/5/8 increased in cells cultured in stiff, stress-relaxing matrices, and pharmacological inhibition of SMAD 1/5/8 activation reduced expression of KDM4B and KDM6B. Together, our results establish novel impacts of stem cell mechanotransduction signaling events that promote osteogenesis through epigenetic remodeling.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar39"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147434265","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