Actin Cytoskeleton and Membrane Interactions: Role in GPCR Function and Organization

Abstract

Cell signaling networks are generally initiated at the cell membrane and mediated by receptors such as  the G protein-coupled receptors (GPCRs).  Adjacent to cell membrane lies a complex network of proteins- the actin cytoskeleton, and several structural and physiological  roles have been attributed to it.  An emerging role of the cytoskeleton is to modulate GPCR function and organization, either directly or
indirectly.  The GPCR-cytoskeleton cross-talk is a complex hierarchical process where each step has its own set of  rules and combinations. Due to the inherent complexity involved at each step and the multiple spatio-temporal levels, a complete picture is yet to emerge.
In this review article, we provide an overview of actin-membrane interactions and how they modulate  GPCR function and organization.
In this context, we briefly discuss the structural characterization of actin monomers and filaments together with their interactions with partner proteins, such as the actin binding proteins.  The effect of actin interactions on membrane domains is examined that assumes significance in light of membrane modulated effects in GPCR function. Direct effects of actin that arise from its role in GPCR organization have been reported from fluorescence aniostropy measurements and theoretical modeling studies.  We envision that this overview will help to bring together concepts in GPCR signaling and cytoskeletal dynamics towards a comprehensive understanding of GPCR function.