Functional interactions between the extracellular domain and the seven-transmembrane domain in Ca2+ receptor activation

O. M. Hauache, J. Hu, K. Ray, A. M. Spiegel

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


We studied the activity of mutants involving the amino-terminal extracellular, seven-transmembrane (7TM) and carboxy-terminal tail domains of the human Ca2+ receptor to gain insight into the functional interactions between these domains during receptor activation. Missense mutations of highly conserved residues, D190 and E297, in the extracellular domain (ECD), and a mutation within part of the proximal carboxy-terminal tail, A877-880E, resulted in receptors with severely reduced response to Ca2+ despite adequate cell surface expression. Coexpression of either D190A or E297K mutants with A877-880E led to significant reconstitution of function. No such reconstitution occurred when D190A or E297K mutants were coexpressed with a truncation mutant possessing an intact amino-terminal extracellular and first transmembrane domain, despite evidence for heterodimerization and cell surface expression of the respective mutant receptors. In addition, no reconstitution of function was observed when D190A was coexpressed with a deletion Ca2+ receptor mutant lacking only a cysteinerich region located in the ECD of the Ca2+ receptor (Ca-//-Ca). Moreover, coexpression of this Ca-//-Ca with A877-880E did not recover function. The results show that Ca2+ receptor extracellular and 7TM domains are discrete entities that can communicate within the context of a heterodimer composed of complementary mutant receptors. Two intact 7TM domains and two intact cysteine-rich regions appear to be required for such communication to occur. The results are discussed in the context of a speculative model of receptor structure and function.

Original languageEnglish (US)
Pages (from-to)63-70
Number of pages8
Issue number1
StatePublished - 2000
Externally publishedYes


  • Activation
  • Calcium receptor
  • Functional interations

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


Dive into the research topics of 'Functional interactions between the extracellular domain and the seven-transmembrane domain in Ca2+ receptor activation'. Together they form a unique fingerprint.

Cite this