RT Journal Article SR Electronic T1 Homer Proteins Regulate Coupling of Group I Metabotropic Glutamate Receptors to N-Type Calcium and M-Type Potassium Channels JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 7238 OP 7245 DO 10.1523/JNEUROSCI.20-19-07238.2000 VO 20 IS 19 A1 Paul J. Kammermeier A1 Bo Xiao A1 Jian Cheng Tu A1 Paul F. Worley A1 Stephen R. Ikeda YR 2000 UL http://www.jneurosci.org/content/20/19/7238.abstract AB Group I metabotropic glutamate receptors (mGluR1 and 5) couple to intracellular calcium pools by a family of proteins, termed Homer, that cross-link the receptor to inositol trisphosphate receptors. mGluRs also couple to membrane ion channels via G-proteins. The role of Homer proteins in channel modulation was investigated by expressing mGluRs and various forms of Homer in rat superior cervical ganglion (SCG) sympathetic neurons by intranuclear cDNA injection. Expression of cross-linking-capable forms of Homer (Homer 1b, 1c, 2, and 3, termed long forms) occluded group I mGluR-mediated N-type calcium and M-type potassium current modulation. This effect was specific for group I mGluRs. mGluR2 (group II)-mediated inhibition of N-channels was unaltered. Long forms of Homer decreased modulation of N- and M-type currents but did not selectively block distinct G-protein pathways. Short forms of Homer, which cannot self-multimerize (Homer 1a and a Homer 2 C-terminal deletion), did not alter mGluR–ion channel coupling. When coexpressed with long forms of Homer, short forms restored the mGluR1a-mediated calcium current modulation in an apparent dose-dependent manner. Homer 2b induced cell surface clusters of mGluR5 in SCG neurons. Conversely, a uniform distribution was observed when mGluR5 was expressed alone or with Homer short forms. These studies indicate that long and short forms of Homer compete for binding to mGluRs and regulate their coupling to ion channels. In vivo, the immediate early Homer 1a is anticipated to enhance ion channel modulation and to disrupt coupling to releasable intracellular calcium pools. Thus, Homer may regulate the magnitude and predominate signaling output of group I mGluRs.