preprints.org > biology and life sciences > biochemistry and molecular biology > doi: 10.20944/preprints202405.0141.v1

Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Version 1 : Received: 1 May 2024 / Approved: 2 May 2024 / Online: 5 May 2024 (08:33:01 CEST)

The first member of the family, visual arrestin-1, was discovered in the late 1970s. Later the other three mammalian subtypes were identified and cloned. The first described function was regulation of GPCR signaling: arrestins bind active phosphorylated GPCRs, blocking their coupling to G proteins. It was later discovered that receptor-bound and free arrestins interact with numerous proteins, regulating GPCR trafficking and various signaling pathways, including those that determine cell fate. Arrestins have no enzymatic activity, they function by organizing multi-protein complexes and localizing their interaction partners to particular cellular compartments. Today we understand the molecular mechanism of arrestin interactions with GPCRs better than the mechanisms underlying other functions. However, even limited knowledge enabled the construction of signaling-biased arrestin mutants and extraction of biologically active monofunctional peptides from these multifunctional proteins. Manipulation of cellular signaling with arrestin-based tools has research and likely therapeutic potential: re-engineered proteins and their parts can produce effects that conventional small molecule drugs cannot.

Arrestin; GPCR; MAP kinase; microtubules; ubiquitin ligase

Biology and Life Sciences, Biochemistry and Molecular Biology

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