Differential functional interaction of two Vesl/Homer protein isoforms with ryanodine receptor type 1: a novel mechanism for control of intracellular calcium signaling

Cell Calcium. 2003 Aug;34(2):177-84. doi: 10.1016/s0143-4160(03)00082-4.


Vesl/Homer proteins physically link proteins that mediate cellular signaling [Curr. Opin. Neurobiol. 10 (2000) 370; Trends Neurosci. 23 (2000) 80; J. Cell Sci. 113 (2000) 1851] and thereby influence cellular function [Nat. Neurosci. 4 (2001) 499; Nature 411 (2001) 962]. A previous study reported that Vesl-1L/Homer-1c (V-1L) controls the gain of the intracellular calcium activated calcium channel ryanodine receptor type 1 (RyR1) channel [J. Biol Chem. 277 (2002) 44722]. Here, we show that the function of RyR1 is differentially regulated by two isoforms of Vesl-1/Homer-1, V-1L and Vesl-1S/Homer-1a (V-1S). V-1L increases the activity of RyR1 while important regulatory functions and pharmacological characteristics are preserved. V-1S alone had no effect on RyR1, even though, like V-1L, it is directly bound to the channel. However, V-1S dose-dependently decreased the effects of V-1L on RyR1, providing a novel mechanism for the regulation of intracellular calcium channel activity and calcium homeostasis by changing expression levels of Vesl/Homer proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Calcium / metabolism*
  • Calcium Signaling*
  • Carrier Proteins / metabolism*
  • Cyclic ADP-Ribose / pharmacology
  • Homer Scaffolding Proteins
  • Muscle, Skeletal / metabolism
  • Neuropeptides / metabolism*
  • Protein Isoforms / metabolism
  • Rats
  • Ryanodine Receptor Calcium Release Channel / metabolism*
  • Sarcoplasmic Reticulum / metabolism


  • Carrier Proteins
  • Homer Scaffolding Proteins
  • Homer1 protein, rat
  • Neuropeptides
  • Protein Isoforms
  • Ryanodine Receptor Calcium Release Channel
  • Cyclic ADP-Ribose
  • Calcium