Nature Neuroscience
6, 1153 - 1161 (2003)
Published online: 5 October 2003; | doi:10.1038/nn1134
PI3 kinase enhancer−Homer complex couples mGluRI to PI3 kinase, preventing neuronal apoptosisRong Rong1, Jee-Yin Ahn1, Honglian Huang1, Eiichiro Nagata2, Daniel Kalman1, Judith A Kapp1, Jiancheng Tu2, Paul F Worley2, Solomon H Snyder2
& Keqiang Ye11
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Room 145, Whitehead Building, 615 Michael Street, Atlanta, Georgia 30322, USA. 2
Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, USA.
Correspondence should be addressed to Keqiang Ye kye@emory.eduPhosphoinositide 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 (mGluRIs) enhances formation of an mGluRI-Homer-PIKE-L 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 mGluRI to prevent neuronal apoptosis.
|
