Tubulin, actin and heterotrimeric G proteins: Coordination of signaling and structure

Abstract

G proteins mediate signals from membrane G protein coupled receptors to the cell interior, evoking significant regulation of cell physiology. The cytoskeleton contributes to cell morphology, motility, division, and transport functions. This review will discuss the interplay between heterotrimeric G protein signaling and elements of the cytoskeleton. Also described and discussed will be the interplay between tubulin and G proteins that results in atypical modulation of signaling pathways and cytoskeletal dynamics. This will be extended to describe how tubulin and G proteins act in concert to influence various aspects of cellular behavior.

Synthetic Lethal Screens Identify Vulnerabilities in GPCR Signaling and Cytoskeletal Organization in E-Cadherin–Deficient Cells

“…Notably, this enrichment was greater for hits that showed minimal impact on the viability of the E-cadherin-expressing MCF10A cells, suggesting that drug targeting of GPCR signaling in CDH1-mutant tumors may be a means to obtain clinical gain while minimizing collateral damage to normal tissues. The nature of the synthetic lethal relationship between E-cadherin and GPCR signaling is not yet known, although the functional diversity of the candidate synthetic lethal GPCR signaling proteins would suggest that the interaction involves a common downstream mechanism such as interplay with the actin and microtubule cytoskeletons (31)(32)(33). The importance of cytoskeletal functions to the E-cadherin synthetic lethal phenotype is supported by the abundance of cytoskeletal genes associated with synthetic lethality in our primary siRNA screen.…”

Proteomic analysis of differentially expressed proteins in the marine fish parasitic ciliate Cryptocaryon irritans

“…Even though there was no direct proof that actin in ciliates could evoke the host immunity against ciliates infection, mice immunized with a recombinant actin-depolymerizing factor (ADF) of C. irritans produced specific antibodies against this protein (Huang et al, 2013). In addition, tubulin and actin could mediate heterotrimeric G protein signal transduction and result to the interplay of signaling pathways and cytoskeletal dynamics, in which the parasite G proteins-coupled receptors were identified as an antigen against host humoral antibodies (Campos et al, 2014;Schappi et al, 2014). Therefore, actin and tubulin, both of which are present in C. irritans, might be utilized as targets for vaccine development to control cryptocaryoniasis.…”

Lateral Diffusion of Gαs in the Plasma Membrane Is Decreased after Chronic but not Acute Antidepressant Treatment: Role of Lipid Raft and Non-Raft Membrane Microdomains

“…These cytosolic Ga s have significantly less scaffolds than their membrane-associated counterparts, which is why we suspect they are able to diffuse at greater speeds. Not surprisingly, they diffuse more slowly still than un-fused GFP, as cytosolic Ga s still has some associations, such as tubulin (Schappi et al, 2014;Yu et al, 2009).…”

“…In the former case, lipid raft integrity requires cholesterol; in the latter, it appears that tubulin structures are involved in the membrane/raft anchoring of Ga s (Schappi et al, 2014). Therefore, we hypothesized that, if rafts constrain Ga s diffusion, raft disruption or microtubule-disrupting agents would also increase half-time of GFP-Ga s FRAP.…”