Molecular Biology of the Cell最新文献

{"title":"WHAMM functions in kidney reabsorption and polymerizes actin to promote autophagosomal membrane closure and cargo sequestration","authors":"Alyssa M Coulter, Valerie Cortés, Corey J Theodore, Rachel E Cianciolo, Ron Korstanje, Kenneth G Campellone","doi":"10.1091/mbc.e24-01-0025","DOIUrl":"https://doi.org/10.1091/mbc.e24-01-0025","url":null,"abstract":"<ul><li><p>The tissue-specific functions of mammalian actin nucleation factors are not well understood.</p></li><li><p>Mice lacking the actin nucleation factor WHAMM show signs of a kidney disease resembling Fanconi Syndrome. Kidneys from WHAMM-deficient male mice display abnormalities in structure and reabsorption function. Cultured proximal tubule cells exhibit defects in autophagosome closure and autophagic cargo sequestration.</p></li><li><p>WHAMM and the Arp2/3 complex are important for nutrient reabsorption in the kidney and autophagosome remodeling in proximal tubule cells.</p></li></ul>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578751","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}

{"title":"Kinesin Regulation in the Proximal Axon is Essential for Dendrite-selective Transport","authors":"Christina S. Mendoza, Cameron R. Plowinske, Andrew C. Montgomery, Geraldine B. Quinones, Gary Banker, Marvin Bentley","doi":"10.1091/mbc.e23-11-0457","DOIUrl":"https://doi.org/10.1091/mbc.e23-11-0457","url":null,"abstract":"<ul><li><p>Dendritic polarity is maintained by the arrest of dendrite-selective vesicles in the proximal axon, but the mechanism that mediates this arrest is unknown.</p></li><li><p>The authors define a new molecular model of kinesin-3 family member KIF13A regulation by MARK2-mediated phosphorylation in the proximal axon. KIF13A is then recognized by 14-3-3 family members, resulting in kinesin-vesicle dissociation and termination of anterograde transport.</p></li><li><p>These results indicate that regulation of kinesin binding to dendritic vesicles, rather than vesicle capture, is the key regulatory event that terminates anterograde transport of dendrite-selective vesicles at the base of the axon.</p></li></ul>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140587565","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}

{"title":"The bistable mitotic switch in fission yeast","authors":"Béla Novák, John J. Tyson","doi":"10.1091/mbc.e24-03-0142","DOIUrl":"https://doi.org/10.1091/mbc.e24-03-0142","url":null,"abstract":"<ul><li><p>Based on their elegant experiments, Patterson et al. (eLife, 2021) concluded that the G2/M transition in fission yeast is controlled by a bistable switch, but we question that conclusion.</p></li><li><p>Using detailed stochastic simulations, we show that the coexisting low and high Cdk1 activity states observed by Patterson et al. can be reproduced by either an irreversible/bistable or a reversible/ultrasensitive switch, and our analysis shows why the experiments of Patterson et al. are inconclusive.</p></li><li><p>We suggest a decisive experiment to distinguish unequivocally between an irreversible/bistable and a reversible/ultrasensitive switch.</p></li></ul>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578726","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}

{"title":"Neurofilament Biophysics: from Structure to Biomechanics","authors":"Erika A. Ding, Sanjay Kumar","doi":"10.1091/mbc.e23-11-0438","DOIUrl":"https://doi.org/10.1091/mbc.e23-11-0438","url":null,"abstract":"<p>Neurofilaments (NFs) are multi-subunit, neuron-specific intermediate filaments consisting of a 10-nm diameter filament “core” surrounded by a layer of long intrinsically disordered protein (IDP) “tails.” NFs are thought to regulate axonal caliber during development and then stabilize the mature axon, with NF subunit misregulation, mutation, and aggregation featuring prominently in multiple neurological diseases. The field's understanding of NF structure, mechanics, and function has been deeply informed by a rich variety of biochemical, cell biological, and mouse genetic studies spanning more than four decades. These studies have contributed much to our collective understanding of NF function in axonal physiology and disease. In recent years, however, there has been a resurgence of interest in NF subunit proteins in two new contexts: as potential blood- and cerebrospinal fluid-based biomarkers of neuronal damage, and as model IDPs with intriguing properties. Here we review established principles and more recent discoveries in NF structure and function. Where possible, we place these findings in the context of biophysics of NF assembly, interaction, and contributions to axonal mechanics.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140587388","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}

{"title":"N-terminal signals in the SNX-BAR paralogs Vps5 and Vin1 guide endosomal coat complex formation","authors":"Shawn P. Shortill, Mia S. Frier, Michael Davey, Elizabeth Conibear","doi":"10.1091/mbc.e24-01-0043","DOIUrl":"https://doi.org/10.1091/mbc.e24-01-0043","url":null,"abstract":"<ul><li><p>The assembly of BAR domain-containing endosomal coats such as retromer involves BAR-BAR pairing, though recent work suggests that additional structural features contribute to subunit selection</p></li><li><p>We identified features in the unstructured N-termini of two paralogous yeast SNX-BARs, Vps5 and Vin1, that mediate the specific formation of the related retromer and VINE complexes</p></li><li><p>Our findings highlight how disordered regions in SNX-BARs help determine the composition of sorting complexes, thereby clarifying mechanisms of modular membrane coat assembly</p></li></ul>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578627","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}

{"title":"Antiparallel microtubule bundling supports KIF15-driven mitotic spindle assembly","authors":"Brittany M. Salazar, Ryoma Ohi","doi":"10.1091/mbc.e24-01-0023","DOIUrl":"https://doi.org/10.1091/mbc.e24-01-0023","url":null,"abstract":"<p>The spindle is a bipolar microtubule-based machine that is crucial for accurate chromosome segregation. Spindle bipolarity is generated by Eg5 (a kinesin-5), a conserved motor that drives spindle assembly by localizing to and sliding apart antiparallel microtubules. In the presence of Eg5 inhibitors (K5Is), KIF15 (a kinesin-12) can promote spindle assembly, resulting in K5I-resistant cells (KIRCs). However, KIF15 is a less potent motor than Eg5, suggesting that other factors may contribute to spindle formation in KIRCs. Protein Regulator of Cytokinesis 1 (PRC1) preferentially bundles antiparallel microtubules, and we previously showed that PRC1 promotes KIF15-microtubule binding, leading us to hypothesize that PRC1 may enhance KIF15 activity in KIRCs. Here, we demonstrate that 1) loss of PRC1 in KIRCs decreases spindle bipolarity, 2) overexpression of PRC1 increases spindle formation efficiency in KIRCs, 3) overexpression of PRC1 protects K5I naïve cells against the Eg5 inhibitor STLC, and 4) PRC1 overexpression promotes the establishment of K5I resistance. These effects are not fully reproduced by a TPX2, a microtubule bundler with no known preference for microtubule orientation. These results suggest a model wherein PRC1-mediated bundling of microtubules creates a more favorable microtubule architecture for KIF15-driven mitotic spindle assembly in the context of Eg5 inhibition.</p><strong>Movie S1: </strong>HeLa KIRCEB3‐GFP by DIC and GFP. HeLa KIRCEB3‐GFP cells were imaged every 5 minutes for 190 minutes. Video shows DIC images taken at a single focal plane and a maximum z‐projection of images taken in the FITC (GFP) channel. Scale bar, 10μm.Download Original Video (.5 MB)<input name=\"cloudFlareScript\" type=\"hidden\" value=\"https://embed.videodelivery.net/embed/sdk.latest.js\"/>\u0000<script>\u0000window.addEventListener('load', function () { var script = document.querySelector('script[src=\"https://embed.videodelivery.net/embed/sdk.latest.js\"]'); if(script === null) { var s = document.createElement('script'); s.type = 'text/javascript'; s.defer = 'defer'; s.src = \"https://embed.videodelivery.net/embed/sdk.latest.js\"; document.getElementsByTagName('body')[0].appendChild(s); } });\u0000</script>\u0000<iframe allow=\"accelerometer; gyroscope; autoplay; encrypted-media; picture-in-picture;\" allowfullscreen=\"true\" height=\"640px\" loading=\"lazy\" poster=\"https://videodelivery.net/eyJraWQiOiI3YjgzNTg3NDZlNWJmNDM0MjY5YzEwZTYwMDg0ZjViYiIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiJjODA2MGQ5NGEyZWFjMGIwOWIzM2FiZWJiYTYyYTQ4MiIsImV4cCI6MTcxMjg3MTcwMSwia2lkIjoiN2I4MzU4NzQ2ZTViZjQzNDI2OWMxMGU2MDA4NGY1YmIifQ.BR7ueBAplCypNK6aKew5zBhhX9ocGQvX1U9jJ7W1sF6dtdxMBZufQoUPYVniaegpArEXuYQqlQG_2QZ9efuSwlam2JmolFq6f7dmk4pB9Df8OKdt6h8nHv3kXbFBElyAFeOdo2xgS6f94xgyTpGZi6VxfOTih1gSHq3PGou6BBZQC3j1TfsDs0MGQmHlWumhAf56aDWAM1H4NBezhLJYgwmAirnK4_KByiVYg7xqnbln565QK7OY3Q9_J0GyNYZMJfjAPrUOxFr85QWGhEJVIKrYCfmx-dofSDgINR3Pq7yG7nvuOEyrIwptprsMDtkUi0EQRuvjpBmCThq7h_ooLg/thumbnails/thumbnail.jpg?time=4.75s\" src=\"https:","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578628","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}

{"title":"Bacterial growth dynamics in a rhythmic symbiosis.","authors":"Liu Yang, Susannah Lawhorn, Clotilde Bongrand, James C. Kosmopoulos, Jill Kuwabara, Michael VanNieuwenhze, Mark J. Mandel, M. McFall-Ngai, Edward Ruby","doi":"10.1091/mbc.E24-01-0044","DOIUrl":"https://doi.org/10.1091/mbc.E24-01-0044","url":null,"abstract":"The symbiotic relationship between the bioluminescent bacterium Vibrio fischeri and the bobtail squid Euprymna scolopes serves as a valuable system to investigate bacterial growth and peptidoglycan (PG) synthesis within animal tissues. To better understand the growth dynamics of V. fischeri in the crypts of the light-emitting organ of its juvenile host, we showed that, after the daily dawn-triggered expulsion of most of the population, the remaining symbionts rapidly proliferate for about 6 h. At that point the population enters a period of extremely slow growth that continues throughout the night until the next dawn. Further, we found that PG synthesis by the symbionts decreases as they enter the slow-growing stage. Surprisingly, in contrast to the most mature crypts (i.e., Crypt 1) of juvenile animals, most of the symbiont cells in the least mature crypts (i.e., Crypt 3) were not expelled and, instead, remained in the slow-growing state throughout the day, with almost no cell division. Consistent with this observation, the expression of the gene encoding the PG-remodeling enzyme, L,D-transpeptidase (LdtA), was greatest during the slowly growing stage of Crypt 1 but, in contrast, remained continuously high in Crypt 3. Finally, deletion of the ldtA gene resulted in a symbiont that grew and survived normally in culture, but was increasingly defective in competing against its parent strain in the crypts. This result suggests that remodeling of the PG to generate additional 3-3 linkages contributes to the bacterium's fitness in the symbiosis, possibly in response to stresses encountered during the very slow-growing stage. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text].","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140716789","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}

{"title":"TGFβ overcomes FGF-induced transinhibition of EGFR in lens cells to enable fibrotic secondary cataract.","authors":"J. Vanslyke, Bruce A. Boswell, L. Musil","doi":"10.1091/mbc.E24-01-0040","DOIUrl":"https://doi.org/10.1091/mbc.E24-01-0040","url":null,"abstract":"In order to cause vision-disrupting fibrotic secondary cataract (PCO), lens epithelial cells that survive cataract surgery must migrate to the posterior of the lens capsule and differentiate into myofibroblasts. During this process, the cells become exposed to the FGF that diffuses out of the vitreous body. In normal development, such relatively high levels of FGF induce lens epithelial cells to differentiate into lens fiber cells. It has been a mystery as to how lens cells could instead undergo a mutually exclusive cell fate, namely epithelial to myofibroblast transition, in the FGF-rich environment of the posterior capsule. We and others have reported that the ability of TGFβ to induce lens cell fibrosis requires the activity of endogenous ErbBs. We show here that lens fiber-promoting levels of FGF induce desensitization of ErbB1 (EGFR) that involves its phosphorylation on threonine 669 mediated by both ERK and p38 activity. Transinhibition of ErbB1 by FGF is overcome by a time-dependent increase in ErbB1 levels induced by TGFβ, the activation of which is increased after cataract surgery. Our studies provide a rationale for why TGFβ upregulates ErbB1 in lens cells and further support the receptor as a therapeutic target for PCO.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140717744","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}

{"title":"Scaling of stochastic growth and division dynamics: A comparative study of individual rod-shaped cells in the Mother Machine and SChemostat platforms","authors":"Karl F Ziegler, Kunaal Joshi, Charles S Wright, Shaswata Roy, Will Caruso, Rudro R Biswas, Srividya Iyer-Biswas","doi":"10.1091/mbc.e23-11-0452","DOIUrl":"https://doi.org/10.1091/mbc.e23-11-0452","url":null,"abstract":"<ul><li><p>A variety of microfluidic device designs are widely used to study the behaviors of single bacterial cells between growth conditions, but a quantitative comparison of growth between different devices remained absent.</p></li><li><p>The authors developed a protocol to obtain side-by-side experiments using two different microfluidic approaches, finding that growth rates and interdivision times differ but are precisely compensated by the division ratio distribution.</p></li><li><p>Identical emergent simplicities govern stochastic intergenerational homeostasis of cell sizes across device and experimental configurations. This intercondition scaling law establishes a principled route to draw comparisons of stochastic growth and division dynamics across experimental modalities.</p></li></ul>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140587390","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}

{"title":"Buffer Choice and pH Strongly Influence Phase Separation of SARS-CoV-2 Nucleocapsid with RNA.","authors":"Nina C Kathe, Mihajlo Novakovic, F. H. Allain","doi":"10.1091/mbc.E23-12-0500","DOIUrl":"https://doi.org/10.1091/mbc.E23-12-0500","url":null,"abstract":"The SARS-CoV-2 nucleocapsid (N) protein is crucial for virus replication and genome packaging. N protein forms biomolecular condensates both in vitro and in vivo in a process known as liquid-liquid phase separation (LLPS), but the exact factors regulating LLPS of N protein are not fully understood. Here, we show that pH and buffer choice have a profound impact on LLPS of N protein. The degree of phase separation is highly dependent on the pH of the solution, which is correlated with histidine protonation in N protein. Specifically, we demonstrate that protonation of H356 is essential for LLPS in phosphate buffer. Moreover, electrostatic interactions of buffer molecules with specific amino acid residues are able to alter the net charge of N protein, thus influencing its ability to undergo phase separation in the presence of RNA. Overall, these findings reveal that even subtle changes in amino acid protonation or surface charge caused by the pH and buffer system can strongly influence the LLPS behaviour, and point to electrostatic interactions as the main driving forces of N protein phase separation. Further, our findings emphasize the importance of these experimental parameters when studying phase separation of biomolecules, especially in the context of viral infections where the intracellular milieu undergoes drastic changes and intracellular pH normally decreases.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140746049","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}