Molecular mechanism of GPCR spatial organization at the plasma membrane
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Molecular mechanism of GPCR spatial organization at the plasma membrane. / Kockelkoren, Gabriele; Lauritsen, Line; Shuttle, Christopher G.; Kazepidou, Eleftheria; Vonkova, Ivana; Zhang, Yunxiao; Breuer, Artù; Kennard, Celeste; Brunetti, Rachel M.; D’Este, Elisa; Weiner, Orion D.; Uline, Mark; Stamou, Dimitrios.
I: Nature Chemical Biology, Bind 20, 2024, s. 142-150.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Molecular mechanism of GPCR spatial organization at the plasma membrane
AU - Kockelkoren, Gabriele
AU - Lauritsen, Line
AU - Shuttle, Christopher G.
AU - Kazepidou, Eleftheria
AU - Vonkova, Ivana
AU - Zhang, Yunxiao
AU - Breuer, Artù
AU - Kennard, Celeste
AU - Brunetti, Rachel M.
AU - D’Este, Elisa
AU - Weiner, Orion D.
AU - Uline, Mark
AU - Stamou, Dimitrios
N1 - Publisher Copyright: © 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2024
Y1 - 2024
N2 - G-protein-coupled receptors (GPCRs) mediate many critical physiological processes. Their spatial organization in plasma membrane (PM) domains is believed to encode signaling specificity and efficiency. However, the existence of domains and, crucially, the mechanism of formation of such putative domains remain elusive. Here, live-cell imaging (corrected for topography-induced imaging artifacts) conclusively established the existence of PM domains for GPCRs. Paradoxically, energetic coupling to extremely shallow PM curvature (<1 µm−1) emerged as the dominant, necessary and sufficient molecular mechanism of GPCR spatiotemporal organization. Experiments with different GPCRs, H-Ras, Piezo1 and epidermal growth factor receptor, suggest that the mechanism is general, yet protein specific, and can be regulated by ligands. These findings delineate a new spatiomechanical molecular mechanism that can transduce to domain-based signaling any mechanical or chemical stimulus that affects the morphology of the PM and suggest innovative therapeutic strategies targeting cellular shape. [Figure not available: see fulltext.].
AB - G-protein-coupled receptors (GPCRs) mediate many critical physiological processes. Their spatial organization in plasma membrane (PM) domains is believed to encode signaling specificity and efficiency. However, the existence of domains and, crucially, the mechanism of formation of such putative domains remain elusive. Here, live-cell imaging (corrected for topography-induced imaging artifacts) conclusively established the existence of PM domains for GPCRs. Paradoxically, energetic coupling to extremely shallow PM curvature (<1 µm−1) emerged as the dominant, necessary and sufficient molecular mechanism of GPCR spatiotemporal organization. Experiments with different GPCRs, H-Ras, Piezo1 and epidermal growth factor receptor, suggest that the mechanism is general, yet protein specific, and can be regulated by ligands. These findings delineate a new spatiomechanical molecular mechanism that can transduce to domain-based signaling any mechanical or chemical stimulus that affects the morphology of the PM and suggest innovative therapeutic strategies targeting cellular shape. [Figure not available: see fulltext.].
U2 - 10.1038/s41589-023-01385-4
DO - 10.1038/s41589-023-01385-4
M3 - Journal article
C2 - 37460675
AN - SCOPUS:85164915195
VL - 20
SP - 142
EP - 150
JO - Nature Chemical Biology
JF - Nature Chemical Biology
SN - 1552-4450
ER -
ID: 360603616