A arrestin

The biochemistry of vision, rh, RHODOPSIN Rhk, rhodopsin KINASE A, ARRESTIN GC, GUANYLATE CYCLASE T, TRANSDUCIN PDE, PHOSPHODIESTERASE. 

Fig. 5.7 (A) Arrestin binds to the phosphorylated receptor and deactivates the receptor. (B) Arrestin recruits clathrin to the receptor-arrestin complex and promotes receptor internalization through clathrin-coated pits. Clathrin is like the deck of an aircraft carrier, forming a platform where the receptor-arrestin complex can land . After landing , the receptor-arrestin complex Is transported by the carrier to its destination in the cell. Moreover, arrestin recruits the cytosolic c-Src tyrosine kinase to the arrestin-receptorcomplex and links receptor desensitization to the activation of the MAP kinase signalling pathway. (According to Zuker and Ranganthan. Reproduced with permission of the authors and Science.)...

Homologous desensitization is a form of desensitization which is mediated by agonist-induced activation of the same receptor. G-protein-coupled receptor kinases (GRKs) and arrestins are involved in this process, which leads to an uncoupling of the receptor from its G protein. 

Bleich A, Gelkopf M, Weizman T, et al Benzodiazepine abuse in a methadone maintenance treatment clinic in Israel characteristics and a pharmacotherapeutic approach. Isr J Psychiatry Relat Sci 39 104-112, 2002 Bohn LM, Gainetdinov RR, Lin FT, et al Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence. Nature 408 720— 723, 2000... 

Huttenrauch F, Nitzki A, Lin FT, Honing S, Oppermann M (2002) Beta-arrestin binding to CC chemokine receptor 5 requires multiple C-terminal receptor phosphorylation sites and involves a conserved Asp-Arg-Tyr sequence motif. J Biol Chem 277 30769-30777 Imitola J, Raddassi K, Park KI, Mueller FJ, Nieto M, Teng YD, Frenkel D, Li J, Sidman RL, Walsh CA, Snyder EY, Khoury SJ (2004) Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor lalpha/CXC chemokine receptor 4 pathway. Proc Natl Acad Sci U S A 101 18117-18122... 

McDonald PH, Chow CW, MiUer WE, Laporte SA, Field ME, Lin FT, Davis RJ, Lefkowitz RJ (2000) Beta-arrestin 2 a receptor-regulated MAPK scaffold for the activation of JNK3. Science 290 1574-1577... 

Heterologous desensitisation refers to the desensitisation of the response to one agonist by the application of a different agonist. For example, desensitisation of a response to adrenaline by application of 5-HT is mediated by protein kinase A or protein kinase C because these kinases can phosphorylate receptors which are not occupied by agonist. Phosphorylation disrupts the receptor-G-protein interaction and induces the binding of specific proteins, arrestins which enhance receptors internalisation via clathrin-coated pits. Thus desensitisation of G-protein-coupled receptors results in a decrease in the number of functional receptors on the cell surface. 

Orsini MJ, Parent JL, Mundell SJ, Marchese A, Benovic JL. Trafficking of the HIV coreceptor CXCR4 role of arrestins and identification of residues in the C-terminal tail that mediate receptor internalization. J Biol Chem 1999 274(43) 31076-31086. 

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