Abstract
Arrestins are important intracellular proteins, multifunctional regulators of G-protein-coupled receptor (GPCR) signaling. They form complexes with most GPCRs (following agonist binding and phosphorylation of receptors) and play a central role in the processes of homologous desensitization, sequestration and downregulation of receptors, which lead to termination of G-protein activation.
Humans have ten arrestin subtypes pertaining to two subfamilies, visual/beta arrestins and alpha arrestins. Visual/beta subfamily (which contains four members: rod arrestin, β-arrestin 1, β-arrestin 2 and cone arrestin) was branched from new finding alpha arrestins relatively recently. "Alpha" fits because this subfamily is ancient/ancestral, and it complements the name of the beta class.
The rod and the cone arrestins are expressed in the retina, where they regulate photoreceptor function. The β-arrestins are ubiquitously expressed proteins whose highest levels of expression are in the brain and spleen.
Besides their role in desensitization (and following processes), β-arrestins promote the formation of signaling complexes with tyrosine kinase Src and mitogen-activated protein kinase cascades allowing G-protein-coupled receptors to signal independently from G-protein. They serve as scaffold and adaptor proteins in these cascades and regulate cellular processes such as chemotaxis, apoptosis, and metastasis.
Thus, novel therapies focused on these proteins may prove useful in the treatment of some cancer disorders (for example breast, lung, and colorectal carcinomas), allergic asthma, hypertension, etc.