Here we reveal a novel non-channel function for TRPM8 which unexpectedly acts as a Rap1 GTPase inhibitor, thereby inhibiting EC motility, independently from the pore function. TRPM8 retains Rap1 intracellularly through direct protein-protein interaction preventing thus its cytoplasm-plasma membrane trafficking. In turn, this mechanism impairs the activation of a major inside-out signaling pathway that trigger the conformational activation of integrins and, consequently, cell adhesion, migration, in vitro endothelial tube formation and spheroid sprouting.

TRPM8 Inhibits Endothelial Cell Migration Via A Non-Channel Function By Trapping Small Gtpase Rap1

FIORIO PLA, Alessandra;GENOVA, TULLIO;CAMILLO, CHIARA;BERNARDINI, MICHELA;SCIANNA, MARCO;VALDEMBRI, Donatella;MUNARON, Luca Maria;SERINI, Guido;
2017-01-01

Abstract

Here we reveal a novel non-channel function for TRPM8 which unexpectedly acts as a Rap1 GTPase inhibitor, thereby inhibiting EC motility, independently from the pore function. TRPM8 retains Rap1 intracellularly through direct protein-protein interaction preventing thus its cytoplasm-plasma membrane trafficking. In turn, this mechanism impairs the activation of a major inside-out signaling pathway that trigger the conformational activation of integrins and, consequently, cell adhesion, migration, in vitro endothelial tube formation and spheroid sprouting.
2017
54
Suppl 1
14
14
Fiorio Pla, A.; Genova, T.; Grolez, G.; Camillo, C.; Bernardini, M.; Bokhobza, A.; Richard, E.; Scianna, M.; Lemonnier, L.; Valdembri, D.; Munaron, L....espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1641489
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