Molecular and Cellular Biochemistry

, Volume 310, Issue 1–2, pp 103–110 | Cite as

Calmodulin binding is dispensable for Rem-mediated Ca2+ channel inhibition

  • Robert N. Correll
  • Chunyan Pang
  • Dana M. Niedowicz
  • Jonathan Satin
  • Douglas A. Andres
Article

Abstract

GTPases of the Ras-related RGK family are negative regulators of high voltage-activated (HVA) Ca2+ channel activity. In this study, we examined the role of calmodulin (CaM) association in Rem-mediated Ca2+ channel inhibition. We found that the Rem/CaM interaction is Ca2+-dependent, and that truncation of the Rem C-terminus before position 277 prevents CaM binding. Serial mutagenesis of the Rem C-terminus between residues 265 and 276 to alanine generated two mutants (RemL271A and RemL274A) that displayed reduced CaM binding, and a subset of these mutants displayed significantly lower cell periphery localization than RemWT. However, reductions in CaM association or membrane trafficking did not affect function, as all Rem mutants could completely inhibit Ca2+ channels. The Rem1–275 truncation mutant partially inhibited Ca2+ channel activity despite its inability to bind CaM. Taken together, these studies indicate that CaM association is not essential for either Rem-mediated Ca2+ channel inhibition or plasma membrane localization.

Keywords

Rem GTPase RGK Ras CaV1.2 Voltage-gated calcium channel Calmodulin L-type calcium channel VDCC 

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Copyright information

© Springer Science+Business Media, LLC. 2007

Authors and Affiliations

  • Robert N. Correll
    • 1
  • Chunyan Pang
    • 1
  • Dana M. Niedowicz
    • 1
  • Jonathan Satin
    • 2
  • Douglas A. Andres
    • 1
  1. 1.Department of Molecular and Cellular BiochemistryUniversity of Kentucky College of MedicineLexingtonUSA
  2. 2.Department of PhysiologyUniversity of Kentucky College of MedicineLexingtonUSA

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