title: Dynamic regulation of ryanodine receptor type 1 (RyR1) channel activity by Homer 1.
abstract: Homer, a family of scaffolding proteins originally identified in neurons, is also expressed in skeletal muscle. Previous studies showed that splice variants of Homer 1 (H1) amplify the gain of the ryanodine receptor type 1 (RyR1) channel complex. Using [3H]ryanodine ([3H]Ry) to probe the conformational state of RyR1, the actions of long- and short-forms of H1 are examined singly and in combination. At < or =200 nM, H1 long-forms (H1b or H1c possessing coiled-coil (CC) domains) and short-forms (H1a or H1EVH1 lacking CC domains) enhance specific [3H]Ry binding to RyR1. However, at a concentration > 200 nM, either H1 form completely inhibited [3H]Ry binding. Importantly, the combinations of H1c+H1EVH1, or H1b+H1a acted in an additive manner to enhance or inhibit [3H]Ry-binding activity. H1a and H1c individually or in combination produced the same dynamic pattern in regulating purified RyR1 channels reconstituted in planar lipid bilayers. In combination, their net action on RyR1 channels depends on total concentrations of H1. These data provide a mechanism by which constitutively and transiently expressed H1 forms can tightly regulate RyR1 channel activity in response to changing levels of expression and degradation of H1 proteins.
authors: Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. fengwei@ucdavis.edu
authors: Wei
authors: W
authors: Feng
authors: Jiancheng
authors: J
authors: Tu
authors: Pierre
authors: P
authors: Pouliquin
authors: Elaine
authors: E
authors: Cabrales
authors: Xiaohua
authors: X
authors: Shen
authors: Angela
authors: A
authors: Dulhunty
authors: Paul F
authors: PF
authors: Worley
authors: Paul D
authors: PD
authors: Allen
authors: Isaac N
authors: IN
authors: Pessah
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D000072233:Homer Scaffolding Proteins; D015640:Ion Channel Gating; D011487:Protein Conformation; D020033:Protein Isoforms / Q000378:metabolism; D011817:Rabbits; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D020033:Protein Isoforms; D019837:Ryanodine Receptor Calcium Release Channel
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