Endophilin recruitment drives membrane curvature generation through coincidence detection of GPCR loop interactions and negative lipid charge.

Autor:	Mondal S; Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Narayan KB; Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Powers I; Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Botterbusch S; Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Baumgart T; Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Electronic address: baumgart@sas.upenn.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2021 Jan-Jun; Vol. 296, pp. 100140. Date of Electronic Publication: 2020 Dec 06.
DOI:	10.1074/jbc.RA120.016118
Abstrakt:	Endophilin plays key roles during endocytosis of cellular receptors, including generating membrane curvature to drive internalization. Electrostatic interactions between endophilin's BIN/Amphiphysin/Rvs domain and anionic membrane lipids have been considered the major driving force in curvature generation. However, the SH3 domain of endophilin also interacts with the proline-rich third intracellular loop (TIL) of various G-protein-coupled receptors (GPCRs), and it is unclear whether this interaction has a direct role in generating membrane curvature during endocytosis. To examine this, we designed model membranes with a membrane density of 1400 receptors per μm 2 represented by a covalently conjugated TIL region from the β1-adrenergic receptor. We observed that TIL recruits endophilin to membranes composed of 95 mol% of zwitterionic lipids via the SH3 domain. More importantly, endophilin recruited via TIL tubulates vesicles and gets sorted onto highly curved membrane tubules. These observations indicate that the cellular membrane bending and curvature sensing activities of endophilin can be facilitated through detection of the TIL of activated GPCRs in addition to binding to anionic lipids. Furthermore, we show that TIL electrostatically interacts with membranes composed of anionic lipids. Therefore, anionic lipids can modulate TIL/SH3 domain binding. Overall, our findings imply that an interplay between TIL, charged membrane lipids, BAR domain, and SH3 domain could exist in the biological system and that these components may act in coordination to regulate the internalization of cellular receptors. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu