This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cheng, Z. Articles by Chang, W. Search for Related Content PubMed PubMed Citation Articles by Cheng, Z. Articles by Chang, W.

Type B -Aminobutyric Acid Receptors Modulate the Function of the Extracellular Ca²⁺-Sensing Receptor and Cell Differentiation in Murine Growth Plate Chondrocytes

Endocrine Research Unit (Z.C., C.T., L.R., T.-H.C., M.M.D., D.S., W.C.), Department of Veterans Affairs Medical Center, Department of Medicine, University of California, San Francisco, California 94121; Department of Physiology (M.G., B.B.), Biozentrum/Pharmazentrum, University of Basel, CH-4056 Basel, Switzerland; and Department of Pathology (M.M.), University of California, San Francisco, California 94143

Address all correspondence and requests for reprints to: Wenhan Chang, Endocrine Research Unit, 111N, Department of Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, California 94121. E-mail: Wenhan.Chang{at}ucsf.edu.

Extracellular calcium-sensing receptors (CaRs) and metabotropic or type B -aminobutyric acid receptors (GABA-B-Rs), two closely related members of family C of the G protein-coupled receptor superfamily, dimerize in the formation of signaling and membrane-anchored receptor complexes. We tested whether CaRs and two GABA-B-R subunits (R1 and R2) are expressed in mouse growth plate chondrocytes (GPCs) by PCR and immunocytochemistry and whether interactions between these receptors influence the expression and function of the CaR and extracellular Ca²⁺-mediated cell differentiation. Both CaRs and the GABA-B-R1 and -R2 were expressed in the same zones of the growth plate and extensively colocalized in intracellular compartments and on the membranes of cultured GPCs. The GABA-B-R1 coimmunoprecipitated with the CaR, confirming a physical interaction between the two receptors in GPCs. In vitro knockout of GABA-B-R1 genes, using a Cre-lox recombination strategy, blunted the ability of high extracellular Ca²⁺ concentration to activate phospholipase C and ERK1/2, suppressed cell proliferation, and enhanced apoptosis in cultured GPCs. In GPCs, in which the GABA-B-R1 was acutely knocked down, there was reduced expression of early chondrocyte markers, aggrecan and type II collagen, and increased expression of the late differentiation markers, type X collagen and osteopontin. These results support the idea that physical interactions between CaRs and GABA-B-R1s modulate the growth and differentiation of GPCs, potentially by altering the function of CaRs.

This article has been cited by other articles:

				W. Chang, C. Tu, T.-H. Chen, D. Bikle, and D. Shoback The Extracellular Calcium-Sensing Receptor (CaSR) Is a Critical Modulator of Skeletal Development Sci. Signal., September 2, 2008; 1(35): ra1 - ra1. [Abstract] [Full Text] [PDF]