Heterotrimeric G Proteins and the Regulation of Microtubule Assembly

Abstract

Microtubules (MTs), a major component of cell cytoskeleton, exhibit diverse cellular functions including cell motility, intracellular transport, cell division, and differentiation. These functions of MTs are critically dependent on their ability to polymerize and depo- lymerize. Although a significant progress has been made in identifying cellular factors that regulate microtubule assembly and dynamics, the role of signal transducing mole- cules in this process is not well understood. It has been demonstrated that heterotrimeric G proteins, which are components of G protein-coupled receptor (GPCR) signaling path- way, interact with microtubules and play important roles in regulating assembly/dynam- ics of this cytoskeletal filament. While α subunit of G proteins (Gα) inhibits microtubule assembly and accelerates microtubule dynamics, Gβγ promotes tubulin polymerization. In this chapter, we review the current status of G-protein modulation of microtubules and cellular and physiological aspects of this regulation. Molecular, biochemical, and cel- lular methodologies that have been used to advance this field of research are discussed. Emphasis has been given on G-protein-microtubule interaction in neuronal differentia- tion as significant progress has been made in this field. The outcome from this research reflects the importance of GPCRs in transducing extracellular signals to regulate a variety of microtubule-associated cellular events.