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

Research output: Contribution to journalArticlepeer-review

434 Citations (Scopus)


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
Issue number6
Publication statusPublished - 2003 Sept 19

Bibliographical note

Funding Information:
We would like to acknowledge Mitra Cowan and the JHMI transgenic core facility for assistance with the generation of Homer 1 ko mice. We thank Craig Montell for TRPC1–TRPC6 cDNAs and Dr. Ambudkar (NIH) for TRPC1 antibody. Research was supported by grants from NIDA and NIMH.

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)


Dive into the research topics of 'Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors'. Together they form a unique fingerprint.

Cite this