title: Differential functional interaction of two Vesl/Homer protein isoforms with ryanodine receptor type 1: a novel mechanism for control of intracellular calcium signaling.
abstract: 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.
authors.affiliation: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX 76107, USA.
authors.forename: Sung-Yong
authors.initials: SY
authors.lastname: Hwang
authors.forename: Jiao
authors.initials: J
authors.lastname: Wei
authors.forename: Jens H
authors.initials: JH
authors.lastname: Westhoff
authors.forename: R Scott
authors.initials: RS
authors.lastname: Duncan
authors.forename: Fumiko
authors.initials: F
authors.lastname: Ozawa
authors.forename: Pompeo
authors.initials: P
authors.lastname: Volpe
authors.forename: Kaoru
authors.initials: K
authors.lastname: Inokuchi
authors.forename: Peter
authors.initials: P
authors.lastname: Koulen
mesh_terms: D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002352:Carrier Proteins / Q000378:metabolism*; D036563:Cyclic ADP-Ribose / Q000494:pharmacology; D000072233:Homer Scaffolding Proteins; D018482:Muscle, Skeletal / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; C000606624:Homer1 protein, rat; D009479:Neuropeptides; D020033:Protein Isoforms; D019837:Ryanodine Receptor Calcium Release Channel; D036563:Cyclic ADP-Ribose; D002118:Calcium