Phospholipase Cγ1 controls surface expression of TRPC3 through an intermolecular PH domain

Damian B. Van Rossum; Randen L. Patterson; Sumit Sharma; Roxanne K. Barrow; Michael Kornberg; Donald L. Gill; Solomon H. Snyder

doi:10.1038/nature03340

Phospholipase Cγ1 controls surface expression of TRPC3 through an intermolecular PH domain

Damian B. Van Rossum, Randen L. Patterson, Sumit Sharma, Roxanne K. Barrow, Michael Kornberg, Donald L. Gill, Solomon H. Snyder

Research output: Contribution to journal › Article › peer-review

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Abstract

Many ion channels are regulated by lipids, but prominent motifs for lipid binding have not been identified in most ion channels. Recently, we reported that phospholipase Cγ1 (PLC-γ1) binds to and regulates TRPC3 channels, components of agonist-induced Ca²⁺ entry into cells. This interaction requires a domain in PLC-γ1 that includes a partial pleckstrin homology (PH) domain-a consensus lipid-binding and protein-binding sequence. We have developed a gestalt algorithm to detect hitherto 'invisible' PH and PH-like domains, and now report that the partial PH domain of PLC-γ1 interacts with a complementary partial PH-like domain in TRPC3 to elicit lipid binding and cell-surface expression of TRPC3. Our findings imply a far greater abundance of PH domains than previously appreciated, and suggest that intermolecular PH-like domains represent a widespread signalling mode.

Original language	English (US)
Pages (from-to)	99-104
Number of pages	6
Journal	Nature
Volume	434
Issue number	7029
DOIs	https://doi.org/10.1038/nature03340
State	Published - Mar 3 2005
Externally published	Yes

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title = "Phospholipase Cγ1 controls surface expression of TRPC3 through an intermolecular PH domain",

abstract = "Many ion channels are regulated by lipids, but prominent motifs for lipid binding have not been identified in most ion channels. Recently, we reported that phospholipase Cγ1 (PLC-γ1) binds to and regulates TRPC3 channels, components of agonist-induced Ca2+ entry into cells. This interaction requires a domain in PLC-γ1 that includes a partial pleckstrin homology (PH) domain-a consensus lipid-binding and protein-binding sequence. We have developed a gestalt algorithm to detect hitherto 'invisible' PH and PH-like domains, and now report that the partial PH domain of PLC-γ1 interacts with a complementary partial PH-like domain in TRPC3 to elicit lipid binding and cell-surface expression of TRPC3. Our findings imply a far greater abundance of PH domains than previously appreciated, and suggest that intermolecular PH-like domains represent a widespread signalling mode.",

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AU - Van Rossum, Damian B.

AU - Patterson, Randen L.

AU - Sharma, Sumit

AU - Barrow, Roxanne K.

AU - Kornberg, Michael

AU - Gill, Donald L.

AU - Snyder, Solomon H.

PY - 2005/3/3

Y1 - 2005/3/3

N2 - Many ion channels are regulated by lipids, but prominent motifs for lipid binding have not been identified in most ion channels. Recently, we reported that phospholipase Cγ1 (PLC-γ1) binds to and regulates TRPC3 channels, components of agonist-induced Ca2+ entry into cells. This interaction requires a domain in PLC-γ1 that includes a partial pleckstrin homology (PH) domain-a consensus lipid-binding and protein-binding sequence. We have developed a gestalt algorithm to detect hitherto 'invisible' PH and PH-like domains, and now report that the partial PH domain of PLC-γ1 interacts with a complementary partial PH-like domain in TRPC3 to elicit lipid binding and cell-surface expression of TRPC3. Our findings imply a far greater abundance of PH domains than previously appreciated, and suggest that intermolecular PH-like domains represent a widespread signalling mode.

AB - Many ion channels are regulated by lipids, but prominent motifs for lipid binding have not been identified in most ion channels. Recently, we reported that phospholipase Cγ1 (PLC-γ1) binds to and regulates TRPC3 channels, components of agonist-induced Ca2+ entry into cells. This interaction requires a domain in PLC-γ1 that includes a partial pleckstrin homology (PH) domain-a consensus lipid-binding and protein-binding sequence. We have developed a gestalt algorithm to detect hitherto 'invisible' PH and PH-like domains, and now report that the partial PH domain of PLC-γ1 interacts with a complementary partial PH-like domain in TRPC3 to elicit lipid binding and cell-surface expression of TRPC3. Our findings imply a far greater abundance of PH domains than previously appreciated, and suggest that intermolecular PH-like domains represent a widespread signalling mode.

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Phospholipase Cγ1 controls surface expression of TRPC3 through an intermolecular PH domain

Abstract

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