Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors.
Group I metabotropic glutamate receptors (mGluRs) activate PI turnover and thereby trigger intracellular calcium release. Previously, we demonstrated that mGluRs form natural complexes with members of a family of Homer-related synaptic proteins. Here, we present evidence that Homer proteins form a physical tether linking mGluRs with the inositol trisphosphate receptors (IP3R). A novel proline-rich "Homer ligand" (PPXXFr) is identified in group 1 mGluRs and IP3R, and these receptors coimmunoprecipitate as a complex with Homer from brain. Expression of the IEG form of Homer, which lacks the ability to cross-link, modulates mGluR-induced intracellular calcium release. These studies identify a novel mechanism in calcium signaling and provide evidence that an IEG, whose expression is driven by synaptic activity, can directly modify a specific synaptic function.
Tu
J C
JC
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Xiao
B
B
Yuan
J P
JP
Lanahan
A A
AA
Leoffert
K
K
Li
M
M
Linden
D J
DJ
Worley
P F
PF
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000235:genetics; D015870:Gene Expression; D017781:Genes, Immediate-Early; D018698:Glutamic Acid / Q000494:pharmacology; D000072233:Homer Scaffolding Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007425:Intracellular Membranes / Q000378:metabolism; D008024:Ligands; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011392:Proline / Q000235:genetics*; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors
D015220:Calcium Channels; D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008024:Ligands; D009479:Neuropeptides; D018160:Receptors, Cytoplasmic and Nuclear; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid; D011392:Proline; D020558:GTP Phosphohydrolases; D034281:Dynamins; D002118:Calcium