Is signal transduction modulated by an interaction between heterotrimeric G-proteins and tubulin?

Abstract

Although it is generally accepted that tubulin plays an important role in G-protein-mediated signal transduction in a variety of systems, the mechanism of this phenomenon is not completely understood. G-protein-tubulin interaction at the cell membrane and the cytosol, and the influence of such an interaction on cellular signaling are discussed in this review article. Because the diameter of a microtubule is 25 nm and the plasma membrane is 9-11 nm thick, it is not possible for membrane-associated tubulin to assemble into a complete microtubule in the membrane environment. However, tubulin heterodimers may be able to function in the membrane environment as individual heterodimers or as polymers arranged into short protofilaments. At the cell membrane, membrane-associated tubulin may influence hormone-receptor interaction, receptor-G-protein coupling, and G-protein-effector coupling. Structural proteins, such as tubulin, can participate in cellular signaling by communicating through physical forces. By virtue of its interaction with the submembranous network of cytoskeletal proteins, tubulin, when perturbed in one locus, can transmit large changes in conformations to other points. Thus, GTP binding to membrane-associated tubulin might lead to a conformational change in either receptors or G proteins. This may, in turn, influence the binding of an agonist to its receptor. On the other hand, in the cell cytosol, subsequent to agonist-induced translocation of G-proteins from the membrane compartment to the cytosol, G-proteins may affect microtubule formation. In GH3 and AtT-20 cells (stably expressing TRH receptor), transiently transfected with Gq alpha cDNA, soluble tubulin levels decreased in Gq alpha-transfected GH3 and AtT-20 cells, by 33% and 52%, respectively. These results suggest that G-proteins may have a direct effect on the microtubule function in vivo. Because tubulin and G-protein families are ubiquitous and highly conserved, an interaction between these two protein families may occur in vivo, and this, in turn, can have an impact on signal transduction. However, the physiological significance of this interaction remains to be demonstrated.

Tubulin Anchoring to Glycolipid-enriched, Detergent-resistant Domains of the Neuronal Plasma Membrane

“…Second, the presence of lipid-anchored tubulin within DRF could play a role in signal transduction. In fact, domains are enriched in signal-transducing molecules, G-protein families included (10 -12), and it is known that tubulin is involved in G-protein-mediated signal transduction in a variety of systems (61). The interaction between these two protein families inside domains can affect signal transduction.…”

The differential distribution of acetylated and detyrosinated alpha‐tubulin in the microtubular cytoskeleton and primary cilia of hyaline cartilage chondrocytes

“…Several studies have reported a similar distribution of detyrosinated α-tubulin in a range of cell types (Wheatley et al 1994 ;Poole et al 1997), although the significance of the punctate staining near the cell membrane is not known. Tubulin heterodimers are thought to function in the membrane environment as polymers arranged into short protofilaments (Ravindra, 1997), and if true of chondrocytes, could explain this cortical punctate staining. ID5 is located within the most stable subset of cytoplasmic microtubules (Geuens et al 1986 ;Skoufias et al 1990 ;Thyberg & Moskalewski, 1993), the differentiation and stability of these structures reflecting their importance to the integrity and function of the microtubular cytoskeleton.…”

“…Matrix macromolecules form transmembrane linkages with acetylated and detyrosinated ciliary microtubules, which are structurally linked to the diplosomal centrioles and determine the position of the centrosome and MTOC within the cytoplasm. Microtubules are known to participate in cellular signalling by communicating physical changes in microtubular conformation from one locus in the cell to other regions of the cytoplasm (Ravindra, 1997). It is therefore possible that the primary cilium could ' sense ' the biomechanical and\or physicochemical properties of the matrix and transduce this information into a cellular response mediated via the microtubular cytoskeleton.…”

Hormone-induced subcellular redistribution of trimeric G proteins

“…In a set of experiments on transfected HEK-293 cells, we were able to demonstrate that prolonged treatment with thyrotropin-releasing hormone induced not only downregulation of total cellular G q a/G 11 a but caused a dramatic shift of these proteins from plasma membranes to the high-speed supernatant [48,49,73]. The appearance of G q a/G 11 a in the cytosol fraction of GH3 and AtT-20 cells was reported by Ravindra [74]. Arthur and coworkers [75] have shown that even short-term treatment of MDCK cells with bradykinin leads to translocation of a significant portion of G q a/G 11 a from plasma membranes to the cytosol.…”