Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors

Joseph P Yuan; Kirill Kiselyov; Dong Ming Shin; Jin Chen; Nikolay Shcheynikov; Shin H Kang; Marlin H Dehoff; Martin K Schwarz; Peter H Seeburg; Shmuel Muallem; Paul F Worley

doi:10.1016/s0092-8674(03)00716-5

Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors

Cell. 2003 Sep 19;114(6):777-89. doi: 10.1016/s0092-8674(03)00716-5.

Authors

Joseph P Yuan¹, Kirill Kiselyov, Dong Ming Shin, Jin Chen, Nikolay Shcheynikov, Shin H Kang, Marlin H Dehoff, Martin K Schwarz, Peter H Seeburg, Shmuel Muallem, Paul F Worley

Affiliation

¹ Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

PMID: 14505576
DOI: 10.1016/s0092-8674(03)00716-5

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 IP(3)R. Conversely, stores can induce extracellular calcium to enter the cell through plasma membrane channels, too. How this "reverse" coupling works was unclear, but store IP(3)Rs 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 IP(3)R that is required for the TRP channel to respond to signals. The TRPC1-Homer-IP(3)R 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.

Publication types

Research Support, U.S. Gov't, P.H.S.

MeSH terms

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

Substances

Calcium Channels
Carrier Proteins
Homer Scaffolding Proteins
Inositol 1,4,5-Trisphosphate Receptors
Macromolecular Substances
Neuropeptides
Receptors, Cell Surface
Receptors, Cytoplasmic and Nuclear
TRPC Cation Channels
transient receptor potential cation channel, subfamily C, member 1
Calcium