Copy the page URI to the clipboard
Sallese, Michele
(2000).
DOI: https://doi.org/10.21954/ou.ro.0000ff8a
Abstract
For a number of G protein-coupled receptors (GPCRs) a rapid, and reversible loss of responsiveness occurs upon exposure to agonists (homologous desensitisation). Two types of proteins play a major role in determining homologous desensitisation: G protein-coupled receptor kinases (GRK), (Chuang, 1996a; Krupnik, 1998), which phosphorylate agonist-occupied GPCRs, and the cofactor, (S)-arrestin (Krupnik 1998). The GRK family consists, so far, of six members named GRK 1 to 6 (Bunemann, 1999). GRK4, unlike the other GRKs exists in two splice variants (Sallese 1994) and was thought to be expressed only in testis (Sallese 1994; Ambrose 1992). In the present study one human and two rat splice variants of GRK4 have been identified. The four human isoforms of GRK4 were named GRK4a, GRK4[3, GRK4y, and GRK48. GRK4 expression in the testis is restricted to spermatozoa and germinal cells, where it associates with mitochondria and acrosomal membranes. Using an antibody common to all the GRK4 isoforms, only GRK4y was detectable in human sperm. Moreover, GRK4a can phosphorylate rhodopsin and this is inhibited by calmodulin (CaM) in a calcium dependent manner, whereas the other three isoforms do not phosphorylate rhodopsin and do not interact with CaM. In-situ hybridisation and immunohistochemical analysis showed that GRK4 is also selectively expressed in the somatodendritic part of Purkinje cells. The metabotropic glutamate receptor 1 (mGluRl) has been found to be expressed in sperm and Purkinje cells and to colocalise with GRK4. Studies using an heterologous expression system (HEK293) have shown that mGluRl signalling is regulated by GRKs including GRK4.
CORE (COnnecting REpositories)
CORE (COnnecting REpositories)
