G protein betagamma subunits regulate cell adhesion through Rap1a and its effector Radil.
The activation of several G protein-coupled receptors is known to regulate the adhesive properties of cells in different contexts. Here, we reveal that Gbetagamma subunits of heterotrimeric G proteins regulate cell-matrix adhesiveness by activating Rap1a-dependent inside-out signals and integrin activation. We show that Gbetagamma subunits enter in a protein complex with activated Rap1a and its effector Radil and establish that this complex is required downstream of receptor stimulation for the activation of integrins and the positive modulation of cell-matrix adhesiveness. Moreover, we demonstrate that Gbetagamma and activated Rap1a promote the translocation of Radil to the plasma membrane at sites of cell-matrix contacts. These results add to the molecular understanding of how G protein-coupled receptors impinge on cell adhesion and suggest that the Gbetagamma x Rap1 x Radil complex plays important roles in this process.
Ahmed
Syed M
SM
Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada.
Daulat
Avais M
AM
Meunier
Alexandre
A
Angers
Stephane
S
D002352:Carrier Proteins / Q000378:metabolism*; D002448:Cell Adhesion; D002460:Cell Line; D005109:Extracellular Matrix / Q000378:metabolism; D044387:GTP-Binding Protein beta Subunits / Q000502:physiology*; D044388:GTP-Binding Protein gamma Subunits / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism; D009419:Nerve Tissue Proteins; D021381:Protein Transport; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism*
D002352:Carrier Proteins; C118981:G-protein Beta gamma; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D016023:Integrins; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; C548041:RADIL protein, human; C430803:RAP1A protein, human; D020827:rap1 GTP-Binding Proteins