A family affair: A Ral-exocyst-centered network links Ras, Rac, Rho signaling to control cell migration

Small GTPases
Giulia ZagoMaria Carla Parrini

Abstract

Cell migration is central to many developmental, physiologic and pathological processes, including cancer progression. The Ral GTPases (RalA and RalB) which act down-stream the Ras oncogenes, are key players in the coordination between membrane trafficking and actin polymerization. A major direct effector of Ral, the exocyst complex, works in polarized exocytosis and is at the center of multiple protein-protein interactions that support cell migration by promoting protrusion formation, front-rear polarization, and extra-cellular matrix degradation. In this review we describe the recent advancements in deciphering the molecular mechanisms underlying this role of Ral via exocyst on cell migration. Among others, we will discuss the recently identified cross-talk between Ral and Rac1 pathways: exocyst binds to a negative regulator (the RacGAP SH3BP1) and to the major effector (the Wave Regulatory Complex, WRC) of Rac1, the master regulator of protrusions. Next challenge will be to better characterize the dynamics in space and in time of these molecular interplays, to better understand the pleiotropic functions of Ral in both normal and cancer cells.

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Citations

Mar 8, 2018·BMC Medical Genomics·Alain CalenderUNKNOWN in the frame of GSF (Groupe Sarcoïdose France)
Jun 22, 2019·Scientific Reports·Manish Kumar SinghMaria Carla Parrini
Mar 18, 2020·Cancers·Larissa Kotelevets, Eric Chastre
Jun 16, 2019·The Journal of Cell Biology·Andrea OmmerUeli Suter
Sep 11, 2020·Journal of Developmental Biology·Matthew BuechnerHikmat Al-Hashimi
Oct 22, 2020·PeerJ·Wanwan CaiWuzhou Yuan
May 22, 2021·Cellular and Molecular Life Sciences : CMLS·Fabien BinaméDominique Bagnard
Oct 6, 2021·Molecular Microbiology·Thilina U B HerathKeith Ireton
Nov 24, 2021·The Biochemical Journal·Sunayana DagarSivaram V S Mylavarapu

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Methods Mentioned

BETA
GTPases
biosensor
GTPase
fluorescence microscopy
nucleotide exchange

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