Ca 2 + Regulates Dimerization of the BAR Domain Protein PICK1 and Consequent Membrane Curvature.
| Autor: | Stan GF; School of Biochemistry, University of Bristol, Bristol, United Kingdom., Shoemark DK; School of Biochemistry, University of Bristol, Bristol, United Kingdom., Alibhai D; Wolfson Bioimaging Facility, University of Bristol, Bristol, United Kingdom., Hanley JG; School of Biochemistry, University of Bristol, Bristol, United Kingdom. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in molecular neuroscience [Front Mol Neurosci] 2022 Jun 02; Vol. 15, pp. 893739. Date of Electronic Publication: 2022 Jun 02 (Print Publication: 2022). |
| DOI: | 10.3389/fnmol.2022.893739 |
| Abstrakt: | Bin-Amphiphysin-Rvs (BAR) domain proteins are critical regulators of membrane geometry. They induce and stabilize membrane curvature for processes, such as clathrin-coated pit formation and endosomal membrane tubulation. BAR domains form their characteristic crescent-shaped structure in the dimeric form, indicating that the formation of the dimer is critical to their function of inducing membrane curvature and suggesting that a dynamic monomer-dimer equilibrium regulated by cellular signaling would be a powerful mechanism for controlling BAR domain protein function. However, to the best of our knowledge, cellular mechanisms for regulating BAR domain dimerization remain unexplored. PICK1 is a Ca 2+ -binding BAR domain protein involved in the endocytosis and endosomal recycling of neuronal AMPA receptors and other transmembrane proteins. In this study, we demonstrated that PICK1 dimerization is regulated by a direct effect of Ca 2+ ions via acidic regions in the BAR domain and at the N-terminus. While the cellular membrane tubulating activity of PICK1 is absent under basal conditions, Ca 2+ influx causes the generation of membrane tubules that originate from the cell surface. Furthermore, in neurons, PICK1 dimerization increases transiently following NMDA receptor stimulation. We believe that this novel mechanism for regulating BAR domain dimerization and function represents a significant conceptual advance in our knowledge about the regulation of cellular membrane curvature. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Stan, Shoemark, Alibhai and Hanley.) |
| Databáze: | MEDLINE |
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