Molecular Biology of the Cell最新文献_第8页

Giardia's domed ventral disc architecture is essential for attachment and contributes to epithelial barrier disruption. 贾第鞭毛虫的弓形腹侧椎间盘结构对附着和上皮屏障破坏至关重要。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2025-08-01 Epub Date: 2025-06-11 DOI: 10.1091/mbc.E23-12-0515

K D Hagen, C Nosala, A Müller, N A Hilton, D Holthaus, J D Schulzke, S M Krug, T Hoffmann, M Laue, C Klotz, A Aebischer, S C Dawson

{"title":"Giardia's domed ventral disc architecture is essential for attachment and contributes to epithelial barrier disruption.","authors":"K D Hagen, C Nosala, A Müller, N A Hilton, D Holthaus, J D Schulzke, S M Krug, T Hoffmann, M Laue, C Klotz, A Aebischer, S C Dawson","doi":"10.1091/mbc.E23-12-0515","DOIUrl":"10.1091/mbc.E23-12-0515","url":null,"abstract":"Giardia lamblia is a widespread anaerobic protistan parasite causing significant diarrheal disease worldwide. Giardia trophozoites attach extracellularly to the host gastrointestinal epithelium using a unique microtubule (MT) organelle, the ventral disk. The complex, dome-shaped disk is composed of microribbon-cross-bridge (MR-CB) protein complexes scaffolded onto a spiral MT array. Attachment is dynamic and reversible, facilitating parasite contact and colonization of the gastrointestinal epithelium. To investigate possible contributions of disk-mediated attachment to host pathobiology, we generated a stable quadruple allelic knockout (KO) of an abundant disk-associated protein, MBP, using a new method of CRISPR-mediated gene disruption. MBPKO mutants had flattened crescent- or horseshoe-shaped discs, severe MR-CB defects, and complete phenotypic penetrance off selection. MBP mutants also had aberrant surface contacts and were unable to resist shear forces under fluid flow. Using a human gastrointestinal organoid model, we discovered that MBPKO mutants had a significantly reduced ability to cause the host epithelial barrier breakdown characteristic of wild-type infections. In contrast, the addition of spent medium or lysed parasites had no impact on epithelial barrier breakdown. Overall, this pioneering work provides direct evidence that MBP is required for the domed-disk architecture and that disk-mediated attachment contributes to host pathobiology, specifically epithelial barrier breakdown.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar93"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275395","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

Cvm1 and its paralogue Cvm2 function as a complex at vacuolar membrane contact sites. Cvm1及其平行的Cvm2在液泡膜接触部位起复合体的作用。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2025-08-01 Epub Date: 2025-07-02 DOI: 10.1091/mbc.E25-02-0089

Daniel D Bisinski, Samira Klössel, René Rasche, Leonhard Breitsprecher, Nadine Gehle, Olympia Ekaterini Psathaki, Rodrigo Quiroga, Daniel Kümmel, Ayelén González Montoro

{"title":"Cvm1 and its paralogue Cvm2 function as a complex at vacuolar membrane contact sites.","authors":"Daniel D Bisinski, Samira Klössel, René Rasche, Leonhard Breitsprecher, Nadine Gehle, Olympia Ekaterini Psathaki, Rodrigo Quiroga, Daniel Kümmel, Ayelén González Montoro","doi":"10.1091/mbc.E25-02-0089","DOIUrl":"10.1091/mbc.E25-02-0089","url":null,"abstract":"Membrane contact sites are regions where organelle membranes come together, and serve as platforms for metabolite exchange, process organization, and regulation of organelle dynamics. The yeast vacuole, equivalent to lysosomes in higher eukaryotes, functions as a degradative organelle, storage compartment, and signaling hub, establishing contacts with multiple organelles. We previously identified the protein Cvm1 as a component of vacuole contact sites with mitochondria, the nuclear endoplasmic reticulum (ER), and peroxisomes. Here, we investigate Cvm1-mediated contacts and show that the contacts with mitochondria require the porins Por1 and Por2. Additionally, Cvm1 forms a protein complex with its paralogue Yml020w, which we designate as Cvm2. Bioinformatic analysis predicts that both proteins contain an α/β-hydrolase fold. Notably, the predicted catalytic triad of Cvm2 is essential for its in vivo function, while Cvm1 lacks an active site. Complex formation is necessary for the function of the proteins, and Cvm1 targets the complex to the vacuole by binding phosphatidylinositol-3-phosphate on this membrane. Overexpression of this complex generates extended contacts between the vacuole and the peripheral ER. Collectively, our work describes the novel Cvm1-Cvm2 complex and molecular interactions important for its function as part of vacuolar contact sites.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar104"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553951","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

Loss of negative regulation by HDAC1 and REST contributes to MAD1 overexpression in breast cancer. HDAC1和REST负调控缺失导致乳腺癌中MAD1过表达。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2025-08-01 Epub Date: 2025-06-04 DOI: 10.1091/mbc.E24-12-0582

Sarah E Copeland, Boya Chen, Avtar Roopra, Beth A Weaver

{"title":"Loss of negative regulation by HDAC1 and REST contributes to MAD1 overexpression in breast cancer.","authors":"Sarah E Copeland, Boya Chen, Avtar Roopra, Beth A Weaver","doi":"10.1091/mbc.E24-12-0582","DOIUrl":"10.1091/mbc.E24-12-0582","url":null,"abstract":"Mitotic arrest deficient 1 (MAD1), an essential component of the mitotic spindle assembly checkpoint, is commonly overexpressed in breast cancers where it serves as a marker of poor prognosis. MAD1 overexpression is sufficient to permit nontransformed cells to form orthotopic mammary tumors and to promote tumorigenesis in a recently described mouse model with inducible expression of endogenous Mad1. However, the mechanism of MAD1 up-regulation in cancer is unclear. Here, we report a 440-bp region of the MAD1L1 promoter that confers a repressive phenotype on MAD1L1 transcription. Bioinformatics analysis implicated histone deacetylase 1 (HDAC1) in MAD1L1 transcriptional regulation. Consistent with this, HDAC1 localizes to the MAD1L1 promoter and HDAC inhibition increases MAD1 mRNA and protein expression. The MAD1L1-repressive region contains a partial binding site for RE1-silencing transcription factor (REST), which utilizes HDAC1 as a cofactor. REST overexpression decreases MAD1 expression. Moreover, breast cancer patient samples show a significant negative correlation between REST and MAD1L1 mRNA expression. These results support a model in which an altered transcriptional program downstream of loss of the tumor-suppressor REST, which normally represses MAD1L1 transcription by recruiting HDAC1-containing repressive complexes, contributes to MAD1 overexpression in breast cancer.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar91"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216350","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

Domain-specific N-glycosylation of the adhesion G-protein-coupled receptor ADGRG6 N-terminal fragment regulates trafficking, proteolytic processing, and signaling. 粘附g蛋白偶联受体ADGRG6 n端片段的结构域特异性n-糖基化调节运输、蛋白水解加工和信号传导。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2025-08-01 Epub Date: 2025-07-02 DOI: 10.1091/mbc.E25-02-0060

Anandhu Jayachandran, Prabakaran Annadurai, Manas Upadhyay, Mansi Tiwari, Priyadatha Sajan, Prateek Sibal, Nayonika Chatterjee, Kasturi Pal

{"title":"Domain-specific N-glycosylation of the adhesion G-protein-coupled receptor ADGRG6 N-terminal fragment regulates trafficking, proteolytic processing, and signaling.","authors":"Anandhu Jayachandran, Prabakaran Annadurai, Manas Upadhyay, Mansi Tiwari, Priyadatha Sajan, Prateek Sibal, Nayonika Chatterjee, Kasturi Pal","doi":"10.1091/mbc.E25-02-0060","DOIUrl":"10.1091/mbc.E25-02-0060","url":null,"abstract":"Adhesion G-protein-coupled receptors (aGPCRs) are characterized by long extracellular N-terminus fragments (NTF) with several adhesive domains. Many aGPCRs are cleaved at the GPCR-autoproteolysis site (GPS), enclosed within the larger GPCR-autoproteolysis-inducing (GAIN) domain. Following cleavage at the endoplasmic reticulum (ER), the NTF and C-terminal fragments (CTF) heterodimerize, and the protomer is trafficked to the plasma membrane. ADGRG6 is an aGPCR playing important roles in embryonic development. It is activated by mechanical perturbation of the NTF and several extracellular matrix (ECM) proteins. GPCRs are known to undergo several posttranslational modifications (PTM) that regulate the molecular pharmacology of these receptors. N-glycosylation is an important PTM that regulates GPCR expression, trafficking, ligand binding, and signaling bias. Although ADGRG6 is N-glycosylated, the location of the glycans remains unknown. Furthermore, are there spatial roles of N-glycosylation in ADGRG6 processing, trafficking, and signaling? To address these gaps in knowledge, we used biochemical and cell-biological approaches using cell lines overexpressing wild-type and N-glycosylation mutants of ADGRG6. We demonstrate that specific N-glycan residues in different domains of the NTF of ADGRG6 have distinct roles in ADGRG6 autoproteolysis, furin cleavage, trafficking to the plasma membrane, and cAMP production.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar101"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553952","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

Sense, plug, and seal: proteins as both rapid responders and constitutive barriers supporting organelle compartmentalization. 感觉，堵塞和密封：蛋白质作为快速反应和构成屏障支持细胞器区隔化。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2025-08-01 Epub Date: 2025-07-02 DOI: 10.1091/mbc.E23-08-0307

Megan C King, C Patrick Lusk, Nicholas R Ader

{"title":"Sense, plug, and seal: proteins as both rapid responders and constitutive barriers supporting organelle compartmentalization.","authors":"Megan C King, C Patrick Lusk, Nicholas R Ader","doi":"10.1091/mbc.E23-08-0307","DOIUrl":"10.1091/mbc.E23-08-0307","url":null,"abstract":"Although organellar compartmentalization is primarily established by the delimiting phospholipid bilayer membranes, the contribution of proteins has been less appreciated. Recently, studies across many realms of cell biology have put new focus on the role of proteins in acting as diffusion barriers in contexts where there are constitutive, regulated, or pathological discontinuities in membranes. Here, we synthesize longstanding observations of proteins acting as both barriers to lateral diffusion on membranes and diffusion in three-dimensional space. In particular, we focus on an emerging, conserved two-step paradigm of protein diffusion barriers that rapidly assemble in response to membranous organelle damage: a first phase of coincident sensing and stopgap \"plugging\" by responding repair proteins followed by a second phase of membrane sealing. We highlight recent work exemplifying this sense, plug, and seal paradigm at the postmitotic nuclear envelope and at ruptures of the interphase nuclear envelope, lysosomes, and the plasma membrane. Taken together, we highlight how cells use a variety of constitutive and induced proteinaceous barriers that support the role of biological membranes in defining organelle compartmentalization. Determining the biophysical nature of these barriers, and their means of \"sensing\" membrane rupture, will be an exciting avenue of future investigations.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"pe6"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553955","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

Phosphorylation of Golgin Imh1 by AMPK/Snf1 compromises Golgi compartmentalization by releasing Arl1-Imh1 axis. AMPK/Snf1磷酸化Golgin Imh1通过释放Arl1-Imh1轴损害高尔基区隔化。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2025-08-01 Epub Date: 2025-06-25 DOI: 10.1091/mbc.E25-02-0084

Pei-Juan Cai, Chia-Jung Yu, Fang-Jen S Lee

{"title":"Phosphorylation of Golgin Imh1 by AMPK/Snf1 compromises Golgi compartmentalization by releasing Arl1-Imh1 axis.","authors":"Pei-Juan Cai, Chia-Jung Yu, Fang-Jen S Lee","doi":"10.1091/mbc.E25-02-0084","DOIUrl":"10.1091/mbc.E25-02-0084","url":null,"abstract":"Golgins, coiled-coil proteins, are crucial for Golgi architecture and intracellular transport. Mammals have four GRIP-domain-containing Golgins, while budding yeast has a single conserved Golgin, Imh1. Imh1 is recruited to the Golgi membrane by the active small GTPase Arl1 via its GRIP domain. Despite extensive phosphorylation of Imh1 under various stress conditions observed in previous screenings, the biological significance and regulatory mechanisms of Imh1 phosphorylation remain unclear. This study reveals that Snf1, a yeast AMPK homologue, regulates the dissociation of the Arl1-Imh1 axis from the Golgi during glucose deprivation by phosphorylating Imh1 at Ser606, Ser802, and Ser804. The phosphomimetic mutant Imh1S606D,S802D,S804D mislocalizes away from the Golgi, while the phospho-deficient mutant Imh1S606A,S802A,S804A, prevents this mislocalization in an Arl1-dependent manner under glucose deprivation, indicating that this change is not due to Arl1 inactivation. We also provide evidence that AMPK/Snf1 associates with Imh1 and directly phosphorylates Imh1, resulting in conformational change. Furthermore, we demonstrate that AMPK/Snf1-regulated Imh1 phosphorylation impairs its ability to support SNARE recycling in ypt6Δ mutants and compromises Golgi homeostasis. Collectively, these findings reveal how AMPK/Snf1-mediated phosphorylation drives the disassembly of the Arl1-Imh1 axis from the Golgi in response to low-energy conditions, highlighting the critical role of Imh1 phosphorylation in regulating Golgi function.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar96"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485120","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 C-terminal domain of SEC-10 is fundamental for exocyst function, apical organization, and cell morphogenesis in Neurospora crassa. SEC-10的c端结构域是粗神经孢子虫胞囊功能、根尖组织和细胞形态发生的基础。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2025-08-01 Epub Date: 2025-07-09 DOI: 10.1091/mbc.E25-03-0146

Alfredo Figueroa-Meléndez, Mónica E Cante-Paz, Diego L Delgado-Álvarez, Altair C Hernández, Juan M Martínez-Andrade, Leonora Martínez-Núñez, Baldo Oliva, Adriana M Rico-Ramírez, Daniel Salgado-Bautista, Oriol Gallego, Mary Munson, Meritxell Riquelme

{"title":"The C-terminal domain of SEC-10 is fundamental for exocyst function, apical organization, and cell morphogenesis in Neurospora crassa.","authors":"Alfredo Figueroa-Meléndez, Mónica E Cante-Paz, Diego L Delgado-Álvarez, Altair C Hernández, Juan M Martínez-Andrade, Leonora Martínez-Núñez, Baldo Oliva, Adriana M Rico-Ramírez, Daniel Salgado-Bautista, Oriol Gallego, Mary Munson, Meritxell Riquelme","doi":"10.1091/mbc.E25-03-0146","DOIUrl":"10.1091/mbc.E25-03-0146","url":null,"abstract":"The exocyst complex is crucial for vesicles secretion. In Neurospora crassa, apical growth is determined by the Spitzenkörper (SPK), where secretory vesicles accumulate before fusing with the plasma membrane (PM). Exocyst subunits SEC-3, -5, -6, -8, and -15 localize to the PM of hyphal tips, while EXO-70 and EXO-84 are found at the SPK. The localization of SEC-10 had remained elusive. This study used SEC-10 tagged with green fluorescent protein (GFP) at its N- or C-terminus to investigate its function. Endogenous GFP-tagging of SEC-10 at the N-terminus preserved exocyst function, whereas C-terminal tagging caused growth and polarity defects, including absence of an SPK, indicative of exocyst dysfunction. Nanoscopic deconvolution elucidated discrete exocytic sites at the PM. A sec-10 knockout mutant was only viable in a heterokaryotic state, confirming SEC-10's essential role in hyphal morphogenesis. Mass spectrometry showed fewer exocyst subunits interacting with SEC-10-GFP compared with GFP-SEC-10, highlighting the importance of the SEC-10 C-terminus in exocyst assembly and stability. SEC-10 sequence analysis revealed a disordered glycine-rich loop at the C-terminal region, conserved in some filamentous fungi, that could provide flexibility to this domain. These findings suggest that an unobstructed SEC-10 C-terminus is indispensable for exocyst-mediated vesicle tethering and fusion at the PM.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar102"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591794","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

Proteolytic processing and host nuclear targeting of the novel effector GRA84 in Toxoplasma gondii. 新效应物GRA84在刚地弓形虫中的蛋白水解加工和宿主核靶向。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2025-08-01 Epub Date: 2025-06-04 DOI: 10.1091/mbc.E24-07-0322

Amara C Thind, Andrew J Mead, Justin J Quan, Jihui Sha, James A Wohlschlegel, Peter J Bradley

{"title":"Proteolytic processing and host nuclear targeting of the novel effector GRA84 in Toxoplasma gondii.","authors":"Amara C Thind, Andrew J Mead, Justin J Quan, Jihui Sha, James A Wohlschlegel, Peter J Bradley","doi":"10.1091/mbc.E24-07-0322","DOIUrl":"10.1091/mbc.E24-07-0322","url":null,"abstract":"Toxoplasma gondii and its relative Neospora caninum are apicomplexan pathogens that secrete an array of dense granule proteins into the parasitophorous vacuole and host cell, where they play roles in acquiring nutrients and modulating host cell functions. Here, we characterize the novel GRA protein GRA84 in T. gondii and N. caninum, which is secreted into the PV and exported into the host cell nucleus. Disruption of Toxoplasma GRA84 does not affect in vitro parasite replication or establishment or maintenance of the chronic infection in vivo. We show that this effector uses the MYR translocon to traverse the vacuolar membrane and is dependent on the aspartyl protease ASP5 for its export to the host nucleus. We demonstrate that GRA84 undergoes processing that removes over 90 amino acids from its N-terminus, an event that is independent of ASP5. We also use mutagenesis to disrupt processing and show that maturation is critical for transit across the vacuolar membrane. Taken together, this work identifies GRA84 in both T. gondii and N. caninum and reveals an unusual processing event that is necessary for maturation of the protein and export of the effector into the host cell.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar97"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216361","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

Delamination of epithelia induced by air-liquid interfaces. 气液界面诱导的上皮分层。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2025-08-01 Epub Date: 2025-06-04 DOI: 10.1091/mbc.E24-11-0500

Chunzi Liu, Gerald G Fuller

{"title":"Delamination of epithelia induced by air-liquid interfaces.","authors":"Chunzi Liu, Gerald G Fuller","doi":"10.1091/mbc.E24-11-0500","DOIUrl":"10.1091/mbc.E24-11-0500","url":null,"abstract":"Many epithelial tissues reside at air-liquid interfaces, as exemplified by the ocular epithelium, oral mucosa, and alveolar epithelium. The epithelial interfacial tension imposes a mechanical challenge to tissue homeostasis. However, the interplay between interfacial properties and homeostasis in biological samples has largely been overlooked due to a lack of suitable measurement methods and theoretical developments. Here, we described a surprising observation in which the surface energy at the cell-air interface is sufficient to delaminate a stratified ocular epithelium from its substrate. We demonstrated that the interfacial tension at the epithelium-fluid interfaces can be measured using a modified Schultz's method. The measured value is conceptually and numerically distinctive from the tensile modulus measured by deformation-based methods, such as micropipette aspiration and tissue surface tensiometers. Furthermore, mechanical analysis at the cell-air-liquid triple line during the delamination process revealed a strain-hardening behavior of the epithelial layers. Finally, perturbations on different junctional protein complexes revealed that epithelial mechanical stability requires a delicate balance among cortical tension, focal adhesion, and cell-liquid interfacial tension. Broadly, the modified Schultz's method can be applied to measuring tissue surface tension, and the delamination phenomenon suggests that surface tension is a crucial contributor to tissue mechanical stability.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar90"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216349","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

Force-insensitive myosin-I enhances endocytosis robustness through actin network-scale collective ratcheting. 力不敏感肌球蛋白- 1通过肌动蛋白网络规模集体棘轮增强内吞稳健性。

IF 2.7 3区生物学

Molecular Biology of the Cell Pub Date : 2025-08-01 Epub Date: 2025-05-28 DOI: 10.1091/mbc.E25-03-0147

Michael A Ferrin, Ross T A Pedersen, David G Drubin, Matthew Akamatsu

{"title":"Force-insensitive myosin-I enhances endocytosis robustness through actin network-scale collective ratcheting.","authors":"Michael A Ferrin, Ross T A Pedersen, David G Drubin, Matthew Akamatsu","doi":"10.1091/mbc.E25-03-0147","DOIUrl":"10.1091/mbc.E25-03-0147","url":null,"abstract":"Force production by type-I myosins influences endocytic progression in many cell types. Because different myosin-I isoforms exhibit distinct force-dependent kinetic properties, it is important to investigate how these properties affect endocytic outcomes, and the mechanisms through which myosin-I contributes to endocytosis. To this end, we adapted our agent-based simulations of endocytic actin networks and incorporated nonprocessive, single-headed myosin motors at the base of the endocytic pit. We varied the unbinding rate and the force dependence of myosin unbinding. Our results revealed that the inclusion of myosin motors facilitated endocytic internalization, but only under kinetic regimes with rapid and less force-sensitive unbinding. Conversely, slow or strongly force-dependent unbinding impeded endocytic progression. As membrane tension increased, the boundary between assistive and inhibitory phases shifted, allowing the myosins to assist over larger regions of the kinetic landscape. Myosin-I's contribution to internalization could not be explained by direct force transduction or increased actin assembly. Instead, the myosins collectively bolstered the robustness of internalization by limiting pit retraction.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"br20"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173968","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