Expression patterns of the regulatory proteins G protein-coupled receptor kinase 2 and beta-arrestin 1 during rat postnatal brain development: effect of hypothyroidism.
G protein-coupled receptor kinase 2 (GRK2) and beta-arrestin 1 are key regulatory proteins that modulate the desensitization and resensitization of a wide variety of G protein-coupled receptors (GPCRs) involved in brain functions. In this report, we describe the postnatal developmental profile of the mRNA and protein levels of GRK2 and beta-arrestin 1 in rat brain. The expression levels of GRK2 and beta-arrestin 1 display a marked increase at the second and third week after birth, respectively, consistent with an involvement of these proteins in brain maturation processes. However, the expression attained at birth and during the first postnatal week with respect to adult values (45-70% for GRK2, approximately 30% for beta-arrestin 1) is relatively high compared to that reported for several GPCRs, indicating the existence of changes in the ratio of receptors to their regulatory proteins during brain development. On the other hand, we report that experimental hypothyroidism results in changes in the patterns of expression of GRK2 and beta-arrestin 1 in cerebral cortex, leading to a 25-30% reduction in GRK2 levels at several stages of development. Such changes could help to explain the alterations in GPCR signaling that occur during this pathophysiological condition.
Penela
P
P
Departamento de Biología Molecular, Centro de Biología Molecular 'Severo Ochoa' (CSIC-UAM), Universidad Autónoma de Madrid, Spain.
Alvarez-Dolado
M
M
Muñoz
A
A
Mayor
F
F
D000818:Animals; D000831:Animals, Newborn; D019390:Arrestins / Q000096:biosynthesis* / Q000235:genetics; D001921:Brain / Q000254:growth & development* / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000096:biosynthesis* / Q000235:genetics; D054769:G-Protein-Coupled Receptor Kinase 2; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism*; D015151:Immunoblotting; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012260:Ribonucleases / Q000378:metabolism; D013961:Thyroid Gland / Q000502:physiology; D013997:Time Factors; D051552:beta-Adrenergic Receptor Kinases; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins
C000605256:Arrb1 protein, rat; D019390:Arrestins; D012333:RNA, Messenger; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins; D017868:Cyclic AMP-Dependent Protein Kinases; C496569:Grk2 protein, rat; D051552:beta-Adrenergic Receptor Kinases; D054769:G-Protein-Coupled Receptor Kinase 2; D012260:Ribonucleases