PI3 kinase enhancer-Homer complex couples mGluRI to PI3 kinase, preventing neuronal apoptosis

Rong Rong, Jee Yin Ahn, Honglian Huang, Eiichiro Nagata, Daniel Kalman, Judith A. Kapp, Jiancheng Tu, Paul F. Worley, Solomon H. Snyder, Keqiang Ye*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

253 Citations (Scopus)

Abstract

Phosphoinositide 3 kinase enhancer (PIKE) is a recently identified nuclear GTPase that activates nuclear phosphoinositide 3-kinase (PI3 kinase). We have identified, cloned and characterized a new form of PIKE, designated PIKE-L, which, unlike the nuclear PIKE-S, localizes to both the cytoplasm and the nucleus. We demonstrate physiologic binding of PIKE-L to Homer, an adaptor protein known to link metabotropic glutamate receptors to multiple intracellular targets including the inositol 1,4,5-trisphosphate receptor (IP3R). We show that activation of group I metabotropic glutamate receptors (mGluR1s) enhances formation of an mGluR1-Homer complex, leading to activation of PI3 kinase activity and prevention of neuronal apoptosis. Our findings indicate that this complex mediates the well-known ability of agonists of mGluR1 to prevent neuronal apoptosis.

Original languageEnglish
Pages (from-to)1153-1161
Number of pages9
JournalNature Neuroscience
Volume6
Issue number11
DOIs
Publication statusPublished - Nov 2003
Externally publishedYes

Cite this