Molecular Biology of the Cell最新文献

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Calcium dynamics of skin-resident macrophages during homeostasis and tissue injury. 皮肤驻留巨噬细胞在稳态和组织损伤期间的钙动力学
IF 3.1 3区 生物学
Molecular Biology of the Cell Pub Date : 2024-12-01 Epub Date: 2024-11-13 DOI: 10.1091/mbc.E24-09-0420
Pearl A Leon Guerrero, Jeffrey P Rasmussen, Eric Peterman
{"title":"Calcium dynamics of skin-resident macrophages during homeostasis and tissue injury.","authors":"Pearl A Leon Guerrero, Jeffrey P Rasmussen, Eric Peterman","doi":"10.1091/mbc.E24-09-0420","DOIUrl":"10.1091/mbc.E24-09-0420","url":null,"abstract":"<p><p>Immune cells depend on rapid changes in intracellular calcium activity to modulate cell function. Skin contains diverse immune cell types and is critically dependent on calcium signaling for homeostasis and repair, yet the dynamics and functions of calcium in skin immune cells remain poorly understood. Here, we characterize calcium activity in Langerhans cells, skin-resident macrophages responsible for surveillance and clearance of cellular debris after tissue damage. Langerhans cells reside in the epidermis and extend dynamic dendrites in close proximity to adjacent keratinocytes and somatosensory peripheral axons. We find that homeostatic Langerhans cells exhibit spontaneous and transient changes in calcium activity, with calcium flux occurring primarily in the cell body and rarely in the dendrites. Triggering somatosensory axon degeneration increases the frequency of calcium activity in Langerhans cell dendrites. By contrast, we show that Langerhans cells exhibit a sustained increase in intracellular calcium following engulfment of damaged keratinocytes. Altering intracellular calcium activity leads to a decrease in engulfment efficiency of keratinocyte debris. Our findings demonstrate that Langerhans cells exhibit context-specific changes in calcium activity and highlight the utility of skin as an accessible model for imaging calcium dynamics in tissue-resident macrophages.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"br26"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624064","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
Optical characterization of molecular interaction strength in protein condensates. 蛋白质凝聚体中分子相互作用强度的光学表征。
IF 3.1 3区 生物学
Molecular Biology of the Cell Pub Date : 2024-12-01 Epub Date: 2024-11-13 DOI: 10.1091/mbc.E24-03-0128
Timon Beck, Lize-Mari van der Linden, Wade M Borcherds, Kyoohyun Kim, Raimund Schlüßler, Paul Müller, Titus M Franzmann, Conrad Möckel, Ruchi Goswami, Mark Leaver, Tanja Mittag, Simon Alberti, Jochen Guck
{"title":"Optical characterization of molecular interaction strength in protein condensates.","authors":"Timon Beck, Lize-Mari van der Linden, Wade M Borcherds, Kyoohyun Kim, Raimund Schlüßler, Paul Müller, Titus M Franzmann, Conrad Möckel, Ruchi Goswami, Mark Leaver, Tanja Mittag, Simon Alberti, Jochen Guck","doi":"10.1091/mbc.E24-03-0128","DOIUrl":"10.1091/mbc.E24-03-0128","url":null,"abstract":"<p><p>Biomolecular condensates have been identified as a ubiquitous means of intracellular organization, exhibiting very diverse material properties. However, techniques to characterize these material properties and their underlying molecular interactions are scarce. Here, we introduce two optical techniques-Brillouin microscopy and quantitative phase imaging (QPI)-to address this scarcity. We establish Brillouin shift and linewidth as measures for average molecular interaction and dissipation strength, respectively, and we used QPI to obtain the protein concentration within the condensates. We monitored the response of condensates formed by fused in sarcoma (FUS) and by the low-complexity domain of hnRNPA1 (A1-LCD) to altering temperature and ion concentration. Conditions favoring phase separation increased Brillouin shift, linewidth, and protein concentration. In comparison to solidification by chemical cross-linking, the ion-dependent aging of FUS condensates had a small effect on the molecular interaction strength inside. Finally, we investigated how sequence variations of A1-LCD, that change the driving force for phase separation, alter the physical properties of the respective condensates. Our results provide a new experimental perspective on the material properties of protein condensates. Robust and quantitative experimental approaches such as the presented ones will be crucial for understanding how the physical properties of biological condensates determine their function and dysfunction.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar154"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624068","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 centennial of E.B. Wilson's The Cell in Development and Heredity. E.B. 威尔逊《发育和遗传中的细胞》发表一百周年。
IF 3.1 3区 生物学
Molecular Biology of the Cell Pub Date : 2024-12-01 DOI: 10.1091/mbc.E24-07-0328
Jane Maienschein, Martin Chalfie, Thoru Pederson
{"title":"The centennial of E.B. Wilson's The Cell in Development and Heredity.","authors":"Jane Maienschein, Martin Chalfie, Thoru Pederson","doi":"10.1091/mbc.E24-07-0328","DOIUrl":"10.1091/mbc.E24-07-0328","url":null,"abstract":"<p><p>We review and salute the third edition of E.B. Wilson's \"The Cell in Development and Heredity\" published a century ago, noting its unique features and placing them in context. Brief commentaries from colleagues convey how they have encountered and have been influenced by <i>The Cell</i>. Although soon to be 100 years old, Wilson's 1925 edition is a hallmark of our profession, reminding us of a time when certain scholars were able to advance knowledge with a singularity of both mind and pen. Our purpose is to acknowledge the accomplishment by the man who brought together so many different facets of understanding cells and who many regard as the founder of cell biology in the United States. We reflect on the volume's admirable success and bring together perspectives on why it still matters.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":"35 12","pages":"rt1"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682095","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
EB-SUN, a new microtubule plus-end tracking protein in Drosophila. EB-SUN--果蝇中一种新的微管加端追踪蛋白
IF 3.1 3区 生物学
Molecular Biology of the Cell Pub Date : 2024-12-01 Epub Date: 2024-10-30 DOI: 10.1091/mbc.E24-09-0402
Sun K Kim, Stephen L Rogers, Wen Lu, Brad S Lee, Vladimir I Gelfand
{"title":"EB-SUN, a new microtubule plus-end tracking protein in <i>Drosophila</i>.","authors":"Sun K Kim, Stephen L Rogers, Wen Lu, Brad S Lee, Vladimir I Gelfand","doi":"10.1091/mbc.E24-09-0402","DOIUrl":"10.1091/mbc.E24-09-0402","url":null,"abstract":"<p><p>Microtubule (MT) regulation is essential for oocyte development. In <i>Drosophila</i>, MT stability, polarity, abundance, and orientation undergo dynamic changes across developmental stages. In our effort to identify novel microtubule-associated proteins that regulate MTs in the <i>Drosophila</i> ovary, we identified a previously uncharacterized gene, CG18190, which encodes a novel MT end-binding (EB) protein, which we propose to name EB-SUN. We show that EB-SUN colocalizes with EB1 at growing MT plus-ends in <i>Drosophila</i> S2 cells. Tissue-specific and developmental expression profiles from Paralog Explorer reveal that EB-SUN is predominantly expressed in the ovary and early embryos, while EB1 is ubiquitously expressed. Furthermore, as early as oocyte determination, EB-SUN comets are highly concentrated in oocytes during oogenesis. EB-SUN knockout (KO) results in decreased MT density at the onset of mid-oogenesis (stage 7) and delays oocyte growth during late mid-oogenesis (stage 9). Combining EB-SUN KO with EB1 knockdown (KD) in germ cells significantly further reduces MT density at stage 7. Hatching assays of single protein depletion reveal distinct roles for EB-SUN and EB1 in early embryogenesis, likely due to differences in their expression and binding partners. Notably, all eggs from EB-SUN KO/EB1 KD females fail to hatch, suggesting partial redundancy between these proteins.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar147"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546408","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
After their membrane assembly, Sec18 (NSF) and Sec17 (SNAP) promote membrane fusion. 在膜组装后,Sec18(NSF)和 Sec17(SNAP)会促进膜融合。
IF 3.1 3区 生物学
Molecular Biology of the Cell Pub Date : 2024-12-01 Epub Date: 2024-10-30 DOI: 10.1091/mbc.E24-10-0439
Hongki Song, Karina Lopes, Amy Orr, William Wickner
{"title":"After their membrane assembly, Sec18 (NSF) and Sec17 (SNAP) promote membrane fusion.","authors":"Hongki Song, Karina Lopes, Amy Orr, William Wickner","doi":"10.1091/mbc.E24-10-0439","DOIUrl":"10.1091/mbc.E24-10-0439","url":null,"abstract":"<p><p>The energy that drives membrane fusion can come from either complete SNARE zippering, from Sec17 and Sec18, or both. Sec17 and Sec18 initially form a complex which binds membranes. Sec17, Sec18, and the apolarity of a loop on the N-domain of Sec17 are required for their interdependent membrane association. To determine whether Sec18 and the Sec17 loop apolarity are still required for fusion after their membrane arrival, a hydrophobic transmembrane (TM) anchor was affixed to the N-terminus of Sec17, forming TM-Sec17. Fusion without energy from complete SNARE zippering requires Sec18 as well as either Sec17 or TM-Sec17. Even without the need for membrane targeting, the TM-Sec17 apolar loop strongly stimulates Sec17/18-driven fusion. Thus, Sec18 and the Sec17 apolar loop are first required for membrane targeting, and once bound, drive rapid fusion. Each of these variables-the absence or presence of Sec17, its N-loop apolarity, addition or omission of Sec18, and unimpeded or diminished energy from SNARE zippering-has almost no effect on the amount of <i>trans</i>-SNARE complex, but instead regulates the capacity of docked membranes to fuse.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar150"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546406","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
Regulating transport efficiency through the nuclear pore complex: The role of binding affinity with FG-Nups. 通过核孔复合体调节运输效率:与 FG-Nups 结合亲和力的作用。
IF 3.1 3区 生物学
Molecular Biology of the Cell Pub Date : 2024-12-01 Epub Date: 2024-10-30 DOI: 10.1091/mbc.E24-05-0224
Atsushi Matsuda, Mohammad R K Mofrad
{"title":"Regulating transport efficiency through the nuclear pore complex: The role of binding affinity with FG-Nups.","authors":"Atsushi Matsuda, Mohammad R K Mofrad","doi":"10.1091/mbc.E24-05-0224","DOIUrl":"10.1091/mbc.E24-05-0224","url":null,"abstract":"<p><p>Macromolecules are transported through the nuclear pore complex (NPC) via a series of transient binding and unbinding events with FG-Nups, which are intrinsically disordered proteins anchored to the pore's inner wall. Prior studies suggest that the weak and transient nature of this binding is crucial for maintaining the transported molecules' diffusivity. In this study, we explored the relationship between binding kinetics and transport efficiency using Brownian dynamics simulations. Our results indicate that the duration of binding is a critical factor in regulating transport efficiency. Specifically, excessively short binding durations insufficiently facilitate transport, while overly long durations impede molecular movement. We calculated the optimal binding duration for efficient molecular transport and found that it aligns with other theoretical predictions. Additionally, the calculated value is comparable to experimental measurements of the association timescale between nuclear transport receptors and FG-Nups at a single binding site. Our study provides a quantitative framework that bridges local molecular interactions with overall transport dynamics through the NPC, offering valuable insights into the mechanisms governing selective molecular transport.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar149"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546409","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
PunctaFinder: An algorithm for automated spot detection in fluorescence microscopy images. PunctaFinder:荧光显微镜图像中斑点自动检测算法。
IF 3.1 3区 生物学
Molecular Biology of the Cell Pub Date : 2024-12-01 Epub Date: 2024-11-13 DOI: 10.1091/mbc.E24-06-0254
Hanna M Terpstra, Rubén Gómez-Sánchez, Annemiek C Veldsink, Tegan A Otto, Liesbeth M Veenhoff, Matthias Heinemann
{"title":"PunctaFinder: An algorithm for automated spot detection in fluorescence microscopy images.","authors":"Hanna M Terpstra, Rubén Gómez-Sánchez, Annemiek C Veldsink, Tegan A Otto, Liesbeth M Veenhoff, Matthias Heinemann","doi":"10.1091/mbc.E24-06-0254","DOIUrl":"10.1091/mbc.E24-06-0254","url":null,"abstract":"<p><p>Fluorescence microscopy has revolutionized biological research by enabling the visualization of subcellular structures at high resolution. With the increasing complexity and volume of microscopy data, there is a growing need for automated image analysis to ensure efficient and consistent interpretation. In this study, we introduce PunctaFinder, a novel Python-based algorithm designed to detect puncta, small bright spots, in raw fluorescence microscopy images without image denoising or signal enhancement steps. Furthermore, unlike other available spot detectors, PunctaFinder not only detects puncta, but also defines the cytoplasmic region, making it a valuable tool to quantify target molecule localization in cellular contexts. PunctaFinder is a widely applicable punctum detector and size estimator, as evidenced by its successful detection of Atg9-positive vesicles, lipid droplets, aggregates of a destabilized luciferase mutant, and the nuclear pore complex. Notably, PunctaFinder excels in detecting puncta in images with a relatively low resolution and signal-to-noise ratio, demonstrating its capability to identify dim puncta and puncta of dynamic target molecules. PunctaFinder reliably detects puncta in fluorescence microscopy images where automated analysis was not possible before, providing researchers with an efficient and robust method for punctum quantification in fluorescence microscopy images.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"mr9"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624080","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
AI: A transformative opportunity in cell biology. AI:细胞生物学的变革机遇。
IF 3.1 3区 生物学
Molecular Biology of the Cell Pub Date : 2024-12-01 DOI: 10.1091/mbc.E24-09-0415
Ambrose Carr, Jonah Cool, Theofanis Karaletsos, Donghui Li, Alan R Lowe, Stephani Otte, Sandra L Schmid
{"title":"AI: A transformative opportunity in cell biology.","authors":"Ambrose Carr, Jonah Cool, Theofanis Karaletsos, Donghui Li, Alan R Lowe, Stephani Otte, Sandra L Schmid","doi":"10.1091/mbc.E24-09-0415","DOIUrl":"10.1091/mbc.E24-09-0415","url":null,"abstract":"<p><p>The success of artificial intelligence (AI) algorithms in predicting protein structure and more recently, protein interactions, demonstrates the power and potential of machine learning and AI for advancing and accelerating biomedical research. As cells are the fundamental unit of life, applying these tools to understand and predict cellular function represents the next great challenge. However, given the complexity of cellular structure and function, the diversity of cell types and the dynamic plasticity of cell states, the task will not be easy. To accomplish this challenge, AI models must scale and grow in sophistication, fueled by quantitative, multimodal data linking cell structure (their molecular composition, architecture, and morphology) to cell function (cell type and state). As cell biologists embrace the potential of AI models focused on cell features and functions, they are well positioned to contribute to their development, validate their utility, and perhaps, most importantly, play a leading role in leveraging the powers and insight emerging from the coming wave of cell-scale AI models.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":"35 12","pages":"pe4"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770468","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 TOG5 domain of CKAP5 is required to interact with F-actin and promote microtubule advancement in neurons. CKAP5的TOG5结构域需要与F-肌动蛋白相互作用,并促进神经元中微管的前进。
IF 3.1 3区 生物学
Molecular Biology of the Cell Pub Date : 2024-12-01 Epub Date: 2024-11-06 DOI: 10.1091/mbc.E24-05-0202
Garrett M Cammarata, Burcu Erdogan, Jan Sabo, Yusuf Kayaer, Michaela Dujava Zdimalova, Filip Engström, Urvika Gupta, Jasming Senel, Tara O'Brien, Chiedza Sibanda, Akanksha Thawani, Eric S Folker, Marcus Braun, Zdenek Lansky, Laura A Lowery
{"title":"The TOG5 domain of CKAP5 is required to interact with F-actin and promote microtubule advancement in neurons.","authors":"Garrett M Cammarata, Burcu Erdogan, Jan Sabo, Yusuf Kayaer, Michaela Dujava Zdimalova, Filip Engström, Urvika Gupta, Jasming Senel, Tara O'Brien, Chiedza Sibanda, Akanksha Thawani, Eric S Folker, Marcus Braun, Zdenek Lansky, Laura A Lowery","doi":"10.1091/mbc.E24-05-0202","DOIUrl":"10.1091/mbc.E24-05-0202","url":null,"abstract":"<p><p>Microtubule (MT) and F-actin cytoskeletal cross-talk and organization are important aspects of axon guidance mechanisms, but how associated proteins facilitate this function remains largely unknown. While the MT-associated protein, CKAP5 (XMAP215/ch-TOG), has been best characterized as a MT polymerase, we have recently highlighted a novel role for CKAP5 in facilitating interactions between MT and F-actin <i>in vitro</i> and in embryonic <i>Xenopus laevis</i> neuronal growth cones. However, the mechanism by which it does so is unclear. Here, using <i>in vitro</i> reconstitution assays coupled with total internal reflection fluorescence microscopy, we report that the TOG5 domain of CKAP5 is necessary for its ability to bind to and bundle actin filaments, as well as to cross-link MTs and F-actin <i>in vitro.</i> Additionally, we show that this novel MT/F-actin cross-linking function of CKAP5 is possible even in MT polymerase-incompetent mutants of CKAP5 <i>in vivo</i>. Indeed, CKAP5 requires both MT and F-actin binding, but not MT polymerization, to promote MT-F-actin alignment in growth cones and axon outgrowth. Taken together, our findings provide mechanistic insights into how MT populations penetrate the growth cone periphery through CKAP5-facilitated interaction with F-actin during axon outgrowth and guidance.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"br24"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591312","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 transmembrane domain of the desmosomal cadherin desmoglein-1 governs lipid raft association to promote desmosome adhesive strength. 脱丝体粘附蛋白 desmoglein-1 的跨膜结构域控制着脂质筏的结合,以促进脱丝体的粘附强度。
IF 3.1 3区 生物学
Molecular Biology of the Cell Pub Date : 2024-12-01 Epub Date: 2024-11-06 DOI: 10.1091/mbc.E24-05-0200
Stephanie E Zimmer, William Giang, Ilya Levental, Andrew P Kowalczyk
{"title":"The transmembrane domain of the desmosomal cadherin desmoglein-1 governs lipid raft association to promote desmosome adhesive strength.","authors":"Stephanie E Zimmer, William Giang, Ilya Levental, Andrew P Kowalczyk","doi":"10.1091/mbc.E24-05-0200","DOIUrl":"10.1091/mbc.E24-05-0200","url":null,"abstract":"<p><p>Cholesterol- and sphingolipid-enriched domains called lipid rafts are hypothesized to selectively coordinate protein complex assembly within the plasma membrane to regulate cellular functions. Desmosomes are mechanically resilient adhesive junctions that associate with lipid raft membrane domains, yet the mechanisms directing raft association of the desmosomal proteins, particularly the transmembrane desmosomal cadherins, are poorly understood. We identified the desmoglein-1 (DSG1) transmembrane domain (TMD) as a key determinant of desmoglein lipid raft association and designed a panel of DSG1<sub>TMD</sub> variants to assess the contribution of TMD physicochemical properties (length, bulkiness, and palmitoylation) to DSG1 lipid raft association. Sucrose gradient fractionations revealed that TMD length and bulkiness, but not palmitoylation, govern DSG1 lipid raft association. Further, DSG1 raft association determines plakoglobin recruitment to raft domains. Super-resolution imaging and functional assays uncovered a strong relationship between the efficiency of DSG1<sub>TMD</sub> lipid raft association and the formation of morphologically and functionally robust desmosomes. Lipid raft association regulated both desmosome assembly dynamics and DSG1 cell surface stability, indicating that DSG1 lipid raft association is required for both desmosome formation and maintenance. These studies identify the biophysical properties of desmoglein transmembrane domains as key determinants of lipid raft association and desmosome adhesive function.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar152"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591315","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
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