Membrane interactions of G proteins and other related proteins

Abstract

Guanine nucleotide-binding proteins, G proteins, propagate incoming messages from receptors to effector proteins. They switch from an inactive to active state by exchanging a GDP molecule for GTP, and they return to the inactive form by hydrolyzing GTP to GDP. Small monomeric G proteins, such as Ras, are involved in controlling cell proliferation, differentiation and apoptosis, and they interact with membranes through isoprenyl moieties, fatty acyl moieties, and electrostatic interactions. This protein-lipid binding facilitates productive encounters of Ras and Raf proteins in defined membrane regions, so that signals can subsequently proceed through MEK and ERK kinases, which constitute the canonical MAP kinase signaling cassette. On the other hand, heterotrimeric G proteins undergo co/post-translational modifications in the alpha (myristic and/or palmitic acid) and the gamma (farnesol or geranylgeraniol) subunits. These modifications not only assist the G protein to localize to the membrane but they also help distribute the heterotrimer (Galphabetagamma) and the subunits generated upon activation (Galpha and Gbetagamma) to appropriate membrane microdomains. These proteins transduce messages from ubiquitous serpentine receptors, which control important functions such as taste, vision, blood pressure, body weight, cell proliferation, mood, etc. Moreover, the exchange of GDP by GTP is triggered by nucleotide exchange factors. Membrane receptors that activate G proteins can be considered as such, but other cytosolic, membranal or amphitropic proteins can accelerate the rate of G protein exchange or even activate this process in the absence of receptor-mediated activation. These and other protein-protein interactions of G proteins with other signaling proteins are regulated by their lipid preferences. Thus, G protein-lipid interactions control the features of messages and cell physiology.

Genetic Modification of theSalmonellaMembrane Physical State Alters the Pattern of Heat Shock Response

“…Most cellular functions are highly dependent on the lipid environment that is controlled by proteins in or around membrane. The existence of special lipid regions and lipid rafts has also been used to design specific lipid therapies for the treatment of several human degenerative diseases (16,65).…”

The primary cilium as a cellular receiver: organizing ciliary GPCR signaling

“…2B): the β-sandwich protein Unc119a/b binds a critical subset of myristoylated proteins in the cytoplasm for targeting to the cilium via a transition zone mediated process [38], whereas the related protein Pde6d functions as the carrier of prenylated proteins [39,40]. Importantly, G α subunits are myristoylated and G γ subunits are prenylated [41], suggesting a coordinated delivery of G proteins via these pathways. Indeed, UNC119 is required for ciliary localization of transducin α , the photoreceptor G α [42].…”

Cardiolipin-Mediated Mitochondrial Dynamics and Stress Response inArabidopsis

“…Nonetheless, CFP-DRP3A R273E , but not the three GTPase activity-reduced dominant negative forms of DRP3A, attenuated the peroxisome elongation phenotype in drp3A-2, supporting the conclusion that CL is not as essential to peroxisome fission as to mitochondrial fission. It is well known that membrane lipid composition can modulate membrane-associated protein functions (Marsh, 2008;Vögler et al, 2008). Thus, the mitochondrionspecific presence of CL and CMDs may reflect a mechanism for DRP3 proteins to distinguish mitochondria from peroxisomes.…”