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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Evidence of the Importance of the First Intracellular Loop of Prokineticin Receptor 2 in Receptor Function

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Author(s):
Abreu, Ana Paula [1, 2] ; Noel, Sekoni D. [1] ; Xu, Shuyun [1] ; Carroll, Rona S. [1] ; Latronico, Ana Claudia [2] ; Kaiser, Ursula B. [1]
Total Authors: 6
Affiliation:
[1] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 - USA
[2] Univ Sao Paulo, Sch Med, Teaching Hosp, Dev Endocrinol Unit, Lab Hormones & Mol Genet, BR-05403 Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: MOLECULAR ENDOCRINOLOGY; v. 26, n. 8, p. 1417-1427, AUG 2012.
Web of Science Citations: 18
Abstract

Prokineticin receptors (PROKR) are G protein-coupled receptors (GPCR) that regulate diverse biological processes, including olfactory bulb neurogenesis and GnRH neuronal migration. Mutations in PROKR2 have been described in patients with varying degrees of GnRH deficiency and are located in diverse functional domains of the receptor. Our goal was to determine whether variants in the first intracellular loop (ICL1) of PROKR2 (R80C, R85C, and R85H) identified in patients with hypogonadotropic hypogonadism interfere with receptor function and to elucidate the mechanisms of these effects. Because of structural homology among GPCR, clarification of the role of ICL1 in PROKR2 activity may contribute to a better understanding of this domain across other GPCR. The effects of the ICL1 PROKR2 mutations on activation of signal transduction pathways, ligand binding, and receptor expression were evaluated. Our results indicated that the R85C and R85H PROKR2 mutations interfere only modestly with receptor function, whereas the R80C PROKR2 mutation leads to a marked reduction in receptor activity. Cotransfection of wild-type (WT) and R80C PROKR2 showed that the R80C mutant could exert a dominant negative effect on WT PROKR2 in vitro by interfering with WT receptor expression. In summary, we have shown the importance of Arg80 in ICL1 for PROKR2 expression and demonstrate that R80C PROKR2 exerts a dominant negative effect on WT PROKR2. (Molecular Endocrinology 26: 1417-1427, 2012) (AU)

FAPESP's process: 05/04726-0 - Molecular characterization of congenital endocrine diseases that affect growth and development
Grantee:Ana Claudia Latronico Xavier
Support Opportunities: Research Projects - Thematic Grants