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Homer Binds TRPC Family Channels and Is Required for Gating of TRPC1 by IP3 Receptors

Authors
 Joseph P Yuan  ;  Kirill Kiselyov  ;  Paul F Worley  ;  Shmuel Muallem  ;  Peter H Seeburg  ;  Martin K Schwarz  ;  Marlin H Dehoff  ;  Shin H Kang  ;  Nikolay Shcheynikov  ;  Jin Chen  ;  Dong Ming Shin 
Citation
 CELL, Vol.114(6) : 777-789, 2003 
Journal Title
 CELL 
ISSN
 0092-8674 
Issue Date
2003
MeSH
Animals ; Binding Sites/physiology ; Brain/metabolism ; Calcium/metabolism ; Calcium Channels/genetics ; Calcium Channels/metabolism* ; Calcium Signaling/genetics ; Carrier Proteins/metabolism* ; Cell Membrane/metabolism ; Cells, Cultured ; Homer Scaffolding Proteins ; Inositol 1,4,5-Trisphosphate Receptors ; Ion Channel Gating/physiology* ; Macromolecular Substances ; Membrane Potentials/genetics ; Mice ; Mice, Mutant Strains ; Mutation/genetics ; Neuropeptides/metabolism* ; Patch-Clamp Techniques ; Protein Binding/genetics ; Protein Structure, Tertiary/physiology ; Rats ; Receptors, Cell Surface/metabolism* ; Receptors, Cytoplasmic and Nuclear/metabolism* ; TRPC Cation Channels
Keywords
14505576
Abstract
Receptor signaling at the plasma membrane often releases calcium from intracellular stores. For example, inositol triphosphate (IP3) produced by receptor-coupled phospholipase C activates an intracellular store calcium channel, the IP3R. Conversely, stores can induce extracellular calcium to enter the cell through plasma membrane channels, too. How this “reverse” coupling works was unclear, but store IP3Rs were proposed to bind and regulate plasma membrane TRP cation channels. Here, we demonstrate that the adaptor protein, termed Homer, facilitates a physical association between TRPC1 and the IP3R that is required for the TRP channel to respond to signals. The TRPC1-Homer-IP3R complex is dynamic and its disassembly parallels TRPC1 channel activation. Homer's action depends on its ability to crosslink and is blocked by the dominant-negative immediate early gene form, H1a. Since H1a is transcriptionally regulated by cellular activity, this mechanism can affect both short and long-term regulation of TRPC1 function.
Files in This Item:
T200306887.pdf Download
DOI
10.1016/S0092-8674(03)00716-5
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Shin, Dong Min(신동민) ORCID logo https://orcid.org/0000-0001-6042-0435
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/114582
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