Accessory proteins for heterotrimeric G-protein: Implication in the cardiovascular system

The G-protein signaling system plays an important role in controlling cellular responses to numerous hormones and neurotransmitters involved in homeostasis of the cardiovascular system. In addition to traditional determinants of G-protein signaling such as the G-protein-coupled receptor (GPCR), heterotrimeric G-proteins and effectors, accumulating data indicate the existence of entities that directly regulate the activation status of G-proteins independent of GPCR. To date, there have been a number of reports on accessory proteins that influence GDP dissociation, affect nucleotide exchange at the Galpha subunit, alter subunit interactions within heterotrimeric Galphabetagamma independent of nucleotide exchange, or form complexes with Galpha or Gbetagamma independent of the typical Galphabetagamma heterotrimer. Such proteins may provide an additional signal input to the G-protein signaling system in the absence of GPCR or may act as an alternative binding partner of G-protein subunits serving unknown roles of G-proteins in cells. Accumulating information suggests that accessory proteins for G-proteins are actually involved in the regulation of the signaling system to maintain homeostasis and the dynamic responses to physiological and pathological challenges. It is likely that alterations in signal processing may be achieved by the modulation of signal processing within the cell using accessory proteins for G-proteins. The loss of regulation of this system, leading to inappropriate activation or inactivation of G-protein signaling, is strongly implicated in various human diseases. In this review, we update current information and discuss different accessory proteins for heterotrimeric G-proteins in terms of their involvement in the regulation of the cardiovascular system. Such information may contribute to uncovering mechanisms underlying cardiovascular disease as well as the development of novel therapeutic approaches to human disease.