Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of homer-related, synaptic proteins.
Homer is a neuronal immediate early gene (IEG) that is enriched at excitatory synapses and binds group 1 metabotropic glutamate receptors (mGluRs). Here, we characterize a family of Homer-related proteins derived from three distinct genes. Like Homer IEG (now termed Homer 1a), all new members bind group 1 mGluRs. In contrast to Homer 1a, new members are constitutively expressed and encode a C-terminal coiled-coil (CC) domain that mediates self-multimerization. CC-Homers form natural complexes that cross-link mGluRs and are enriched at the postsynaptic density. Homer 1a does not multimerize and blocks the association of mGluRs with CC-Homer complexes. These observations support a model in which the dynamic expression of Homer 1a competes with constitutively expressed CC-Homers to modify synaptic mGluR properties.
Xiao
B
B
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Tu
J C
JC
Petralia
R S
RS
Yuan
J P
JP
Doan
A
A
Breder
C D
CD
Ruggiero
A
A
Lanahan
A A
AA
Wenthold
R J
RJ
Worley
P F
PF
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D000072233:Homer Scaffolding Proteins; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D014018:Tissue Distribution
D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D018094:Receptors, Metabotropic Glutamate