Protein–Protein Interactions in TRPC Channel Complexes

Screening for homologues of the Drosophila trp (transient receptor potential) gene product has uncovered a large family of membrane proteins of which the closest relatives to the Drosophila protein have been assigned to the canonical or classical subfamily (TRPC). The prominent physiological function of these proteins, as delineated from heterologous expression and knockdown experiments in native cells, appears to be sensing phospholipase C (PLC)–derived stimuli and conversion of this input into cellular Ca2+ signals. Another common feature of TRPC proteins is the ability to form cation-conducting pore structures. Thus, the role of TRPCs in PLC-dependent Ca2+ signaling has been attributed to the formation of regulated Ca2+ entry channels. Despite the existence of this unifying principle of TRPC signal transduction, an unforeseen complexity of the roles of TRPC proteins within the cellular Ca2+ signaling network emerged. The contribution of TRPC proteins to cellular Ca2+homeostasis may involve formation of a wide variety of different Ca2+ entry pathways that contain distinct TRPC homo-or heteromultimeric pore structures, along with a multitude of regulatory proteins and scaffolds. Here, we summarize current knowledge on protein–protein interactions that are of potential significance for the formation and function of native TRPC channel complexes and highlight recent concepts regarding the role of these interactions for cellular control of plasma membrane cation conductances and cellular Ca2+ signaling.