Human Ca2+ receptor cysteine-rich domain: Analysis of function of mutant and chimeric receptors

Jianxin Hu, Omar Hauache, Allen M. Spiegel

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

The 612-residue extracellular domain of the human Ca2+ receptor (hCaR) has been speculated to consist of a Venus's-flytrap domain (VFT) and a cysteine-rich domain. We studied the function of the hCaR Cys-rich domain by using mutagenesis and chimera approaches. A chimeric hCaR with the sequence from residues 540-601 replaced by the corresponding sequence from the Fugu CaR remained fully functional. Another chimetic hCaR with the same region of sequence replaced by the corresponding sequence from metabotropic glutamate receptor subtype 1 (mGluR1) still was activated by extracellular Ca2+ ([Ca2+](o)), but its function was severely compromised. Chimeric receptors with the hCaR VFT and mGluR1 seven-transmembrane domain plus C-tail domain retained good response to [Ca2+](o) whether the Cys-rich domain was from hCaR or from mGluR1. Mutant hCaR with the Cys-rich domain deleted failed to respond to [Ca2+](o), although it was expressed at the cell surface and capable of dimerization. Our results indicate that the hCaR Cys-rich domain plays a critical role in signal transmission from VFT to seven-transmembrane domain. This domain tolerates a significant degree of amino acid substitution and may not be directly involved in the binding of [Ca2+](o).

Original languageEnglish (US)
Pages (from-to)16382-16389
Number of pages8
JournalJournal of Biological Chemistry
Volume275
Issue number21
DOIs
StatePublished - May 26 2000
Externally publishedYes

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Metabotropic Glutamate Receptors
Cysteine
Droseraceae
Mutagenesis
Dimerization
Substitution reactions
Amino Acids
Takifugu
Amino Acid Substitution
Tail

ASJC Scopus subject areas

  • Biochemistry

Cite this

Human Ca2+ receptor cysteine-rich domain : Analysis of function of mutant and chimeric receptors. / Hu, Jianxin; Hauache, Omar; Spiegel, Allen M.

In: Journal of Biological Chemistry, Vol. 275, No. 21, 26.05.2000, p. 16382-16389.

Research output: Contribution to journalArticle

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