Thyroid hormone regulation of rhes, a novel Ras homolog gene expressed in the striatum

Citation
P. Vargiu et al., Thyroid hormone regulation of rhes, a novel Ras homolog gene expressed in the striatum, MOL BRAIN R, 94(1-2), 2001, pp. 1-8
Citations number
30
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
MOLECULAR BRAIN RESEARCH
ISSN journal
0169-328X → ACNP
Volume
94
Issue
1-2
Year of publication
2001
Pages
1 - 8
Database
ISI
SICI code
0169-328X(20011019)94:1-2<1:THRORA>2.0.ZU;2-T
Abstract
Thyroid hormone action on brain development is essentially exerted through regulation of the expression rate of a number of genes some of which have b een identified in the past 10 years. In the present work we describe the th yroid hormone regulation of a novel Ras homolog which we have named Rhes (R as homolog enriched in striatum). The rhes cDNA was previously isolated in subtractive hybridization experiments aimed at identifying cDNA clones corr esponding to genes expressed preferentially in the rat striatum. The sequen ce was found to encode a small GTP-binding protein of the Ras family with h ighest homology to the dexamethasone-inducible Dexras1. Here we show that r hes mRNA and protein in the striatum are strongly dependent on the thyroida l status. Developmentally, Rhes was regulated such that in normal rats ther e was an increased rhes mRNA content in the striatum, after postnatal day 5 (P5). Rhes concentration in hypothyroid rats was similar to that of normal rats at P5, but the subsequent age-dependent increase was blunted. The adm inistration of a single T3 dose to hypothyroid rats normalized rhes mRNA co ncentration in 8 h, whereas it took 24 h, or more, to normalize the express ion of rc3, another T3-dependent brain gene, involved in PKC signaling. Dou ble in situ hybridization using rhes and rc3 riboprobes showed that the bul k of rhes signal was located in cells expressing rc3. Given the relevance o f small GTPases in signal transduction it is very likely that control of rh es, in addition to rc3, is of relevance to explain the actions of thyroid h ormone in the striatum, a region of the brain especially vulnerable in neur ological cretinism. (C) 2001 Elsevier Science BY. All rights reserved.