G protein Signaling, Journeys Beyond the Plasma Membrane

Abstract

G proteins classically associated with the 7TM or serpentine
receptors generally exist as a heterotrimeric complex consisting of α,
β and γ subunits. These proteins serve as transducers of extracellular
signal from plasma membrane to cellular interior. Binding of G proteincoupled
receptor (GPCR) with a ligand leads to their activation, followed
by that of Gα, which then dissociates from Gβγ subunits and initiate
downstream effects through plasma membrane-localized effectors. This
plasma membrane-restricted view of G proteins was challenged when
they were found to be present in various intracellular locations such
as endomembranes, cytoskeleton, mitochondria, and nucleus thereby
opening up newer spatial domains for the action of these signaling molecules.
Many recent studies have addressed the spatiotemporal dynamics
underlying this atypical distribution and the G proteins have been
shown to undergo activation-dependent as well as activation-independent
relocalization. This spatially ‘directed’ targeting of G proteins provides
them rapid access to intracellular communication network without
relying on diffusible second messengers. Here, we present a consolidated
review of the existing knowledge about the presence and physiological
roles for G proteins in these atypical locations, along with the
mechanistic knowhow presently known about underlying processes.