G Protein Trafficking

Wedegaertner, Philip

doi:10.1007/978-94-007-4765-4_11

Cited by 32 publications

(32 citation statements)

References 131 publications

(200 reference statements)

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“…Heterotrimeric G proteins have long been recognized at intracellular membrane locations as well as at the plasma membrane (reviewed in [22,23]), but it is largely unknown if internal heterotrimeric G proteins are substrates for activation by GPCRs. Because G protein subunits present on internal membranes can themselves redistribute and functionally interact with membrane trafficking machineries, the presence of activated G proteins on internal membranes would not necessarily require their direct activation at these sites.…”

Section: Evidence For G Protein-dependent Signaling From Intracellulamentioning

confidence: 99%

GPCR signaling along the endocytic pathway

Irannejad¹,

Zastrow²

2014

Current Opinion in Cell Biology

183

153

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Many G protein-coupled receptors (GPCRs) internalize after agonist-induced activation. While endocytosis has long been associated with homeostatic attenuation of cellular responsiveness, accumulating evidence from study of a wide range of eukaryotes reveals that the endocytic pathway also contributes to generating receptor-initiated signals themselves. Here we review recent progress in this area, discussing primarily but not exclusively GPCR signaling in mammalian cells.

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Section: Evidence For G Protein-dependent Signaling From Intracellulamentioning

confidence: 99%

GPCR signaling along the endocytic pathway

Irannejad¹,

Zastrow²

2014

Current Opinion in Cell Biology

183

153

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“…Activity-dependent translocation of G␣ and G␤␥ subunits occurs in other cells as well (4,5), most notably for G␣ s , the subunit responsible for stimulation of adenylate cyclase. Stimulation of a cognate receptor or inhibition of GTPase activity promotes activation and translocation of G␣ s from the plasma membrane to the cell interior (6 -8).…”

mentioning

confidence: 99%

Activated G Protein Gαs Samples Multiple Endomembrane Compartments

Martin

Lambert

2016

Journal of Biological Chemistry

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Heterotrimeric G proteins are localized to the plasma membrane where they transduce extracellular signals to intracellular effectors. G proteins also act at intracellular locations, and can translocate between cellular compartments. For example, G␣ s can leave the plasma membrane and move to the cell interior after activation. However, the mechanism of G␣ s translocation and its intracellular destination are not known. Here we use bioluminescence resonance energy transfer (BRET) to show that after activation, G␣ s rapidly associates with the endoplasmic reticulum, mitochondria, and endosomes, consistent with indiscriminate sampling of intracellular membranes from the cytosol rather than transport via a specific vesicular pathway. The primary source of G␣ s for endosomal compartments is constitutive endocytosis rather than activity-dependent internalization. Recycling of G␣ s to the plasma membrane is complete 25 min after stimulation is discontinued. We also show that an acylation-deacylation cycle is important for the steady-state localization of G␣ s at the plasma membrane, but our results do not support a role for deacylation in activity-dependent G␣ s internalization.Heterotrimeric G proteins are best known for their role in transducing signals from the extracellular environment across the plasma membrane (1). However, it is becoming increasingly apparent that these signaling molecules have important functions in other cellular locations (2). Therefore, it is important to know how G proteins are distributed among various intracellular compartments, and how these proteins traffic between the plasma membrane, the cytosol, cytoskeletal elements, and intracellular organelles both in their resting state and when they are activated.The most well studied example of activity-dependent G protein trafficking occurs in the retina, where intense illumination promotes the dissociation of transducin from rod outer segment disks and the subsequent translocation of both G␣ t and G␤␥ into the rod inner segment (3). Activity-dependent translocation of G␣ and G␤␥ subunits occurs in other cells as well (4, 5), most notably for G␣ s , the subunit responsible for stimulation of adenylate cyclase. Stimulation of a cognate receptor or inhibition of GTPase activity promotes activation and translocation of G␣ s from the plasma membrane to the cell interior (6 -8).One important yet poorly understood aspect of G␣ s internalization is the intracellular destination of this G protein. Cell fractionation studies have shown that a large amount of constitutively active G␣ s is found in the soluble fraction, suggesting that active G␣ s may simply become soluble in the cytosol (8, 9). However, only a small amount of G␣ s enters the soluble fraction after receptor-mediated activation, consistent with vesicle-mediated internalization and continued association with membranes. Imaging studies have shown that internalized G␣ s can appear to be diffuse in the cytosol (8, 9), but association with intracellular vesicles has also been observed (10 -12)...

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“…These factors include: (1) lipid modifications and other membrane targeting domains present on the subunits; (2) heterotrimer composition, (3) local membrane environment; (4) other accessory binding partners such as RGS proteins or scaffolds; (5) the presence or absence of downstream effector(s), and (6) receptor coupling. Each Gα subunit relies upon a unique combination of multiple N-terminal covalent lipid modifications (myristoylation and/or palmitoylation) alone or in concerted action with adjacent charged polybasic patches to confer varying strengths of membrane anchoring and subunit targeting within the plasma membrane 11 . Gγ subunits, when bound to their inseparable partner Gβ, also contain distinct combinations of C-terminal lipid modification (farnesylation or geranyl-geranylation).…”

mentioning

confidence: 99%

“…Gγ subunits, when bound to their inseparable partner Gβ, also contain distinct combinations of C-terminal lipid modification (farnesylation or geranyl-geranylation). Together, these confer to the G protein heterotrimer capacity for membrane anchoring and selective coupling to GPCRs 11 . The unique combination of lipids and Gα and Gβγ pairing provide varying strengths of membrane anchoring as well as constraints on protein diffusion.…”

mentioning

confidence: 99%

G protein coupled receptor signaling complexes in live cells

Hepler¹

2014

Cellular Logistics

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Classical models of receptor (GPCR) and G protein (Gαβγ) signaling based on biochemical studies have proposed that receptor stimulation results in G protein activation (Gα-GTP) and dissociation of the heterotrimer (Gα-GTP + Gβγ) to regulate downstream signaling events. Unclear is whether or not there exists freely diffusible, activated Gα-GTP on cellular membranes capable of catalytic signal amplification. Recent studies in live cells indicate that GPCRs serve as platforms for the assembly of macromolecular signaling complexes that include G proteins to support a highly efficient and spatially restricted signaling event, with no requirement for full Gα-GTP and Gβγ dissociation and lateral diffusion within the plasma membrane.

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G Protein Trafficking

Cited by 32 publications

References 131 publications

GPCR signaling along the endocytic pathway

GPCR signaling along the endocytic pathway

Activated G Protein Gαs Samples Multiple Endomembrane Compartments

G protein coupled receptor signaling complexes in live cells

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