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

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

Research output: Contribution to journalArticle

396 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)777-789
Number of pages13
JournalCell
Volume114
Issue number6
DOIs
Publication statusPublished - 2003 Sep 19

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Inositol 1,4,5-Trisphosphate Receptors
Cell membranes
Cell Membrane
Calcium
Transient Receptor Potential Channels
Immediate-Early Genes
Type C Phospholipases
Inositol
Calcium Channels
Ion Channels
Genes
Chemical activation
Association reactions
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Yuan, J. P., Kiselyov, K., Shin, D., Chen, J., Shcheynikov, N., Kang, S. H., ... Worley, P. F. (2003). Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors. Cell, 114(6), 777-789. https://doi.org/10.1016/S0092-8674(03)00716-5
Yuan, Joseph P. ; Kiselyov, Kirill ; Shin, DongMin ; Chen, Jin ; Shcheynikov, Nikolay ; Kang, Shin H. ; Dehoff, Marlin H. ; Schwarz, Martin K. ; Seeburg, Peter H. ; Muallem, Shmuel ; Worley, Paul F. / Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors. In: Cell. 2003 ; Vol. 114, No. 6. pp. 777-789.
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Yuan, JP, Kiselyov, K, Shin, D, Chen, J, Shcheynikov, N, Kang, SH, Dehoff, MH, Schwarz, MK, Seeburg, PH, Muallem, S & Worley, PF 2003, 'Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors', Cell, vol. 114, no. 6, pp. 777-789. https://doi.org/10.1016/S0092-8674(03)00716-5

Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors. / Yuan, Joseph P.; Kiselyov, Kirill; Shin, DongMin; Chen, Jin; Shcheynikov, Nikolay; Kang, Shin H.; Dehoff, Marlin H.; Schwarz, Martin K.; Seeburg, Peter H.; Muallem, Shmuel; Worley, Paul F.

In: Cell, Vol. 114, No. 6, 19.09.2003, p. 777-789.

Research output: Contribution to journalArticle

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AU - Shcheynikov, Nikolay

AU - Kang, Shin H.

AU - Dehoff, Marlin H.

AU - Schwarz, Martin K.

AU - Seeburg, Peter H.

AU - Muallem, Shmuel

AU - Worley, Paul F.

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