Cell. 2003 Sep 19;114(6):777-89.
Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors.
Yuan, J. P., Kiselyov, K., Shin, D. M., Chen, J., Shcheynikov, N., Kang, S. H., Dehoff, M. H., Schwarz, M. K., Seeburg, P. H., Muallem, S., Worley, P. F.,
["Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."]
["Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."]
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.
PMID: 14505576

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Screening
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Experimental screening | Non-experimental screening | Reference | ||||||||
TRP channel construct | Interactor source | |||||||||
TRP channel | Interactor | Method | Species | Region | Species | Organ/tissue | Sample type | |||
TRPC1 |
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Homer-1 | Inference | Prediction | 14505576 | |||||
TRPC1 |
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Homer-2 | Inference | Prediction | 14505576 | |||||
TRPC1 |
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Homer-3 | Inference | Prediction | 14505576 | |||||
TRPC2 |
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Homer-1 | Inference | Prediction | 14505576 | |||||
TRPC4 |
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Homer-3 | Inference | Prediction | 14505576 | |||||
TRPC5 |
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Homer-1 | Inference | Prediction | 14505576 | |||||
TRPC5 |
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Homer-3 | Inference | Prediction | 14505576 |
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

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Validation: In vitro validation
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Assay with recombinant proteins | Reference | |||||||||
TRP channel construct | Interactor construct | |||||||||
TRP channel | Interactor | Method | Species | Region | Expression system | Species | Region | Expression system | ||
TRPC1 |
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Homer-3 | Fusion protein-pull down assay | Not used | Rat cerebellum lysates | Not specified | Full-length | E. coli | 14505576 |
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

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Validation: In vivo validation
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Assay with endogenous proteins | Assay with overexpressed proteins | Reference | ||||||||
Cell or tissue | Cell or tissue | TRP channel construct | Interactor construct | |||||||
TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
TRPC1 |
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Homer-1 | Co-immunoprecipitation | HEK293 | Human | Full-length | Not used | 14505576 | ||
TRPC1 |
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Homer-1 | Co-immunoprecipitation | Rat brain hippocampus | 14505576 | |||||
TRPC1 |
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Homer-2 | Co-immunoprecipitation | HEK293 | Human | Full-length | Not used | 14505576 | ||
TRPC1 |
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Homer-3 | Co-immunoprecipitation | HEK293 | Human | Full-length | Not used | 14505576 | ||
TRPC1 |
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Homer-3 | Co-immunoprecipitation | Rat cerebellum lysates | 14505576 | |||||
TRPC1 |
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IP3R3 | Co-immunoprecipitation | HEK293 | Human | Full-length | Not used | 14505576 | ||
TRPC2 |
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Homer-1 | Co-immunoprecipitation | HEK293 | Mouse | Full-length | Not used | 14505576 | ||
TRPC2 |
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IP3R3 | Co-immunoprecipitation | HEK293 | Mouse | Full-length | Not used | 14505576 | ||
TRPC3 |
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IP3R3 | Co-immunoprecipitation | HEK293 | Human | Full-length | Not used | 14505576 | ||
TRPC4 |
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Homer-3 | Co-immunoprecipitation | HEK293 | Mouse | Full-length | Not used | 14505576 | ||
TRPC4 |
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IP3R3 | Co-immunoprecipitation | HEK293 | Mouse | Full-length | Not used | 14505576 | ||
TRPC5 |
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Homer-1 | Co-immunoprecipitation | HEK293 | Mouse | Full-length | Not used | 14505576 | ||
TRPC5 |
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Homer-3 | Co-immunoprecipitation | HEK293 | Mouse | Full-length | Not used | 14505576 | ||
TRPC5 |
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IP3R3 | Co-immunoprecipitation | HEK293 | Mouse | Full-length | Not used | 14505576 | ||
TRPC6 |
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IP3R3 | Co-immunoprecipitation | HEK293 | Human | Full-length | Not used | 14505576 |
(
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

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Characterization
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Binding region mapping | Stoichiometry | Affinity (Kd) | Reference | |||||||
TRP channel | Interactor | |||||||||
TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
TRPC1 |
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Homer-3 | Co-immunoprecipitation | Human | 645-648 | Human | EVH1 domain | 14505576 | ||
TRPC1 |
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Homer-3 | Fusion protein-pull down assay | Human | 20-23 | Not specified | EVH1 domain | 14505576 | ||
TRPC1 |
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IP3R3 | Co-immunoprecipitation | Human | 645-648 | Human | Not determined | 14505576 |
(
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
