Plethora of functions packed into 45  kDa arrestins: biological implications and possible therapeutic strategies.

Plethora of functions packed into 45 kDa arrestins: biological implications and possible therapeutic strategies. Cell Mol Life Sci. 2019 Aug 17;: Authors: Gurevich VV, Gurevich EV Abstract Mammalian arrestins are a family of four highly homologous relatively small ~ 45 kDa proteins with surprisingly diverse functions. The most striking feature is that each of the two non-visual subtypes can bind hundreds of diverse G protein-coupled receptors (GPCRs) and dozens of non-receptor partners. Through these interactions, arrestins regulate the G protein-dependent signaling by the desensitization mechanisms as well as control numerous signaling pathways in the G protein-dependent or independent manner via scaffolding. Some partners prefer receptor-bound arrestins, some bind better to the free arrestins in the cytoplasm, whereas several show no apparent preference for either conformation. Thus, arrestins are a perfect example of a multi-functional signaling regulator. The result of this multi-functionality is that reduction (by knockdown) or elimination (by knockout) of any of these two non-visual arrestins can affect so many pathways that the results are hard to interpret. The other difficulty is that the non-visual subtypes can in many cases compensate for each other, which explains relatively mild phenotypes of single knockouts, whereas double knockout is lethal in vivo, although cultured cells lacking both arrestins are viable. Thus...
Source: Cellular and Molecular Life Sciences : CMLS - Category: Cytology Authors: Tags: Cell Mol Life Sci Source Type: research