Binding of inositol phosphates to arrestin

Abstract

Arrestin binds to phosphorylated rhodopsin in its light‐activated form (metarhodopsin II), blocking thereby its interaction with the G‐protein, transducin. In this study, we show that highly phosphorylated forms of inositol compete against the arrestin‐rhodopsin interaction. Competition curves and direct binding assays with free arrestin consistently yield affinities in the micromolar range; for example, inositol 1,3,4,5‐tetrakisphosphate (InP₄) and inositol hexakisphosphate (InP₆ bind to arrestin with dissociation constants of 12 μM and 5 μM, respectively. Only a small control amount of inositol phosphates is bound, when arrestin interacts with phosphorylated rhodopsin. This argues for a release of bound inositol phosphates by interaction with rhodopsin. Transducin, rhodopsin kinase, or cyclic GMP phosphodiesterase are not affected by inositol phosphates. These observations open a new way to purify arrestin and to inhibit its interaction with rhodopsin. Their physiological significance deserves further investigation.