The classical visual and β-arrestins belong to a larger family of proteins that likely share structural similarity. Humans have an additional six related proteins sometimes termed the α-arrestins, whose functions are now emerging. Surprisingly, several α-arrestins play prominent roles in the regulation of metabolism and obesity. One α-arrestin, thioredoxin-interacting protein (Txnip), has crucial functions in regulating glucose uptake and glycolytic flux through the mitochondria. Another α-arrestin, Arrdc3, is linked to obesity in men and was recently identified in mice as a regulator of body mass, adiposity, and energy expenditure. Here we discuss recent evidence suggesting potential common themes for all arrestins, including physiological roles for classical arrestins in metabolism and the functions of α-arrestins in receptor signaling and endocytosis.
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