Homer proteins in Ca2+ signaling by excitable and non-excitable cells

Paul F. Worley, Weizhong Zeng, Guojin Huang, Joo Young Kim, Dong Min Shin, Min Seuk Kim, Joseph P. Yuan, Kirill Kiselyov, Shmuel Muallem

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

Homers are scaffolding proteins that bind Ca2+ signaling proteins in cellular microdomains. The Homers participate in targeting and localization of Ca2+ signaling proteins in signaling complexes. However, recent work showed that the Homers are not passive scaffolding proteins, but rather they regulate the activity of several proteins within the Ca2+ signaling complex in an isoform-specific manner. Homer2 increases the GAP activity of RGS proteins and PLCβ that accelerate the GTPase activity of Gα subunits. Homer1 gates the activity of TRPC channels, controls the rates of their translocation and retrieval from the plasma membrane and mediates the conformational coupling between TRPC channels and IP3Rs. Homer1 stimulates the activity of the cardiac and neuronal L-type Ca2+ channels Cav1.2 and Cav1.3. Homer1 also mediates the communication between the cardiac and smooth muscle ryanodine receptor RyR2 and Cav1.2 to regulate E-C coupling. In many cases the Homers function as a buffer to reduce the intensity of Ca2+ signaling and create a negative bias that can be reversed by the immediate early gene form of Homer1. Hence, the Homers should be viewed as the buffers of Ca2+ signaling that ensure a high spatial and temporal fidelity of the Ca2+ signaling and activation of downstream effects.

Original languageEnglish
Pages (from-to)363-371
Number of pages9
JournalCell Calcium
Volume42
Issue number4-5
DOIs
StatePublished - 2007

Keywords

  • CaV1.2
  • Coupling
  • Homer
  • IP receptors
  • Ryanodine receptors
  • TRPC channels

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    Worley, P. F., Zeng, W., Huang, G., Kim, J. Y., Shin, D. M., Kim, M. S., Yuan, J. P., Kiselyov, K., & Muallem, S. (2007). Homer proteins in Ca2+ signaling by excitable and non-excitable cells. Cell Calcium, 42(4-5), 363-371. https://doi.org/10.1016/j.ceca.2007.05.007