Mutational analysis of the cysteines in the extracellular domain of the human Ca2+ receptor: Effects on cell surface expression, dimerization and signal transduction

Gao Feng Fan, Kausik Ray, Xin Mei Zhao, Paul K. Goldsmith, Allen M. Spiegel

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Mammalian calcium receptors (CaRs) share with the metabotropic glutamate receptors (mGluRs) the relative positions of 16 cysteine residues in the amino-terminal extracellular domain. To investigate the role of these cysteines, a series of mutants in the extracellular domain of the human CaR was prepared in which each of these 16 cysteine residues and three others not conserved in the mGluRs were replaced by serines. Wild-type and mutant CaR cDNAs were expressed in HEK-293 cells, and evaluated for expression and response to extracellular calcium. Mutation of three non-conserved cysteines and of two conserved cysteines produced proteins with near wild-type phenotype. In contrast, mutation of the other conserved cysteines gave proteins that showed drastic reduction in cell surface expression and/or failed to respond to calcium. We identified 14 cysteines essential for proper trafficking and function of the receptor, two of which may be involved in formation of a disulfide-linked dimer. Copyright (C) 1998 Federation of European Biochemical Societies.

Original languageEnglish (US)
Pages (from-to)353-356
Number of pages4
JournalFEBS Letters
Volume436
Issue number3
DOIs
StatePublished - Oct 9 1998
Externally publishedYes

Fingerprint

Signal transduction
Dimerization
Cysteine
Signal Transduction
Metabotropic Glutamate Receptors
Calcium
Calcium-Sensing Receptors
Mutation
HEK293 Cells
Disulfides
Dimers
Serine
Proteins
Complementary DNA
Phenotype

Keywords

  • Disulfide
  • G protein-coupled receptor
  • Human calcium receptor

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Mutational analysis of the cysteines in the extracellular domain of the human Ca2+ receptor : Effects on cell surface expression, dimerization and signal transduction. / Fan, Gao Feng; Ray, Kausik; Zhao, Xin Mei; Goldsmith, Paul K.; Spiegel, Allen M.

In: FEBS Letters, Vol. 436, No. 3, 09.10.1998, p. 353-356.

Research output: Contribution to journalArticle

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AU - Spiegel, Allen M.

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