Key phases in the formation of caveolae |
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Affiliation: | 1. The University of Queensland, Institute for Molecular Bioscience, Brisbane, Queensland, 4072, Australia;2. The University of Queensland, Centre for Microscopy and Microanalysis, Brisbane, Queensland, 4072, Australia;1. Department of Cell Biology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06520-8002, USA;2. Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA, 02115, USA;1. Department of Biomedical Engineering, 107 W. Dean Keeton St., C0800, Austin, TX, 78712, USA;2. Institute for Cellular and Molecular Biology, The University of Texas at Austin, Norman Hackerman Building, 100 East 24th St., NHB 4500, Austin, TX, 78712, USA;1. Department of Chemistry, Institute for Biophysical Dynamics, James Franck Institute and Computation Institute, The University of Chicago, Chicago, IL 60637, USA;2. Laboratoire Physico Chimie Curie, Institut Curie, PSL Research University, CNRS UMR168, 75005 Paris, France;3. Sorbonne Universités, UPMC Univ Paris 06, 75005 Paris, France;4. Center for Studies in Physics and Biology, The Rockefeller University, New York, NY 10065, USA |
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Abstract: | Caveolae are abundant plasma membrane pits formed by the coordinated action of peripheral and integral membrane proteins and membrane lipids. Here, we discuss recent studies that are starting to provide a glimpse of how filamentous cavin proteins, membrane-embedded caveolin proteins, and specific plasma membrane lipids are brought together to make the unique caveola surface domain. Protein assembly involves multiple low-affinity interactions that are dependent on ‘fuzzy’ charge-dependent interactions mediated in part by disordered cavin and caveolin domains. We propose that cavins help generate a lipid domain conducive to full insertion of caveolin into the bilayer to promote caveola formation. The synergistic assembly of these dynamic protein complexes supports the formation of a metastable membrane domain that can be readily disassembled both in response to cellular stress and during endocytic trafficking. We present a mechanistic model for generation of caveolae based on these new insights. |
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Keywords: | Caveolae Cavin Caveolin Fuzzy interaction Membrane lipids |
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