Presynaptic clustering of mGluR7a requires the PICK1 PDZ domain binding site.
Aggregation of neurotransmitter receptors at pre- and postsynaptic structures is crucial for efficient neuronal communication. In contrast to the wealth of information about postsynaptic specializations, little is known about the molecular organization of presynaptic membrane proteins. We show here that the metabotropic glutamate receptor mGluR7a, which localizes specifically to presynaptic active zones, interacts in vitro and in vivo with PICK1. Coexpression in heterologous systems induces coclustering dependent upon the extreme C terminus of mGluR7a and the PDZ domain of PICK1. mGluR7a and PICK1 localize to excitatory synapses in hippocampal neurons. Furthermore, whereas transfected mGluR7a clusters at presynaptic sites, mGluR7adelta3 lacking the PICK1 binding site targets to axons but does not cluster. These results suggest that PICK1 is a component of the presynaptic machinery involved in mGluR7a aggregation and in modulation of glutamate neurotransmission.
Boudin
H
H
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Doan
A
A
Xia
J
J
Shigemoto
R
R
Huganir
R L
RL
Worley
P
P
Craig
A M
AM
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D008164:Luminescent Proteins / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D020033:Protein Isoforms / Q000737:chemistry; D017434:Protein Structure, Tertiary / Q000235:genetics; D051381:Rats; D011940:Receptor Aggregation / Q000235:genetics*; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D008164:Luminescent Proteins; D009687:Nuclear Proteins; C498298:PICK1 protein, rat; D020033:Protein Isoforms; D018094:Receptors, Metabotropic Glutamate; C102719:metabotropic glutamate receptor 7; D049452:Green Fluorescent Proteins