Arrestin2 expression selectively increases during neural differentiation.
Arrestins and G protein-coupled receptor kinases (GRKs) are key players in homologous desensitization of G protein-coupled receptors. Two non-visual arrestins, arrestin2 and 3, and five GRKs (GRK2, 3, 4, 5 and 6) are involved in desensitization of many receptors. Here, we demonstrate a steady increase in arrestin2 expression during prenatal development. The density of arrestin2 mRNA is higher in differentiated areas as compared with proliferative zones, whereas arrestin3 mRNA shows the opposite distribution. At embryonic day 14, concentrations of arrestin proteins are similar (32-34 nM). Later in development, arrestin2 expression rises, leading to a fourfold excess of arrestin2 over arrestin3 at birth (48 vs. 11 ng/mg protein or 102 vs. 25 nM). Among GRKs, only GRK5 increased with embryonic age from 124 nm at E14 to 359 nM at birth. Similarly, in vitro differentiation of cultured precursor cells, neurospheres, leads to a significant up-regulation of arrestin2 resulting in > 20-fold excess of arrestin2 (160 vs. 7 nM). GRK5 is the only subtype increased with neurosphere differentiation, although the change is only about twofold. The data demonstrate selective increases in the expression of arrestin2 associated with neural development and suggest specific yet unappreciated roles for arrestin2 in neural differentiation.
Gurevich
Eugenia V
EV
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA. Eugenia.Gurevich@vanderbilt.edu
Benovic
Jeffrey L
JL
Gurevich
Vsevolod V
VV
D000818:Animals; D019390:Arrestins / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000196:embryology; D002454:Cell Differentiation / Q000502:physiology; D003342:Corpus Striatum / Q000196:embryology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D047108:Embryonic Development; D054774:G-Protein-Coupled Receptor Kinase 5; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000378:metabolism; D023282:Nuclease Protection Assays; D010750:Phosphoproteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012260:Ribonucleases; D018874:Spheroids, Cellular / Q000378:metabolism; D015854:Up-Regulation
D019390:Arrestins; D007527:Isoenzymes; D010750:Phosphoproteins; C082333:arrestin3; D017346:Protein Serine-Threonine Kinases; D054774:G-Protein-Coupled Receptor Kinase 5; C517897:Grk5 protein, rat; D012260:Ribonucleases