Endophilin recruitment drives membrane curvature generation through coincidence detection of GPCR loop interactions and negative lipid charge
| Autor: | Samsuzzoha Mondal, Samuel Botterbusch, Tobias Baumgart, Imania Powers, Karthik B. Narayan |
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| Rok vydání: | 2021 |
| Předmět: |
DOPS
1 2-dioleoyl-sn-glycero-3-phospho-L-serine Membrane lipids ROI region of interest CIE clathrin-independent endocytosis chemical and pharmacologic phenomena CME clathrin-mediated endocytosis Biochemistry BAR BIN/Amphiphysin/Rvs src Homology Domains PC phosphatidylcholine GPCR endophilin GPCRs G-protein-coupled receptors Receptors Adrenergic beta Humans endocytosis BAR domain Protein Interaction Domains and Motifs TEM transmission electron microscopy CD circular dichroism Molecular Biology adrenergic receptor GUVs giant unilamellar vesicles G protein-coupled receptor Chemistry Cell Membrane FRAP fluorescence recovery after photobleaching WPI World Precision Instruments hemic and immune systems Cell Biology Receptor-mediated endocytosis Lipids DOPC 1 2-dioleoyl-sn-glycero-3-phosphocholine Protein Transport FEME fast endophilin-mediated endocytosis PRDs proline-rich domains Membrane TIL third intracellular loop Membrane curvature membrane curvature Amphiphysin Biophysics Proline-Rich Protein Domains SDP sulfodichlorophenol ITO indium tin oxide Membrane biophysics Acyltransferases Research Article |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.ra120.016118 |
| Popis: | 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 μm2 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. |
| Databáze: | OpenAIRE |
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