Presynaptic clustering of mGluR7a requires the PICK1PDZ domain binding site

Aggregation of neurotransmitter receptors at pre- and postsynaptic structur es is crucial for efficient neuronal communication. In contrast to the weal th 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 specifica lly to presynaptic active zones, interacts in vitro and in vivo with PICK1. Coexpression in heterologous systems induces coclustering dependent upon t he extreme C terminus of mGluR7a and the PDZ domain of PICK1, mGluR7a and P ICK1 localize to excitatory synapses in hippocampal neurons. Furthermore, w hereas transfected mGluR7a clusters at presynaptic sites, mGluR7a Delta3 la cking the PICK1 binding site targets to axons but does not cluster. These r esults suggest that PICK1 is a component of the presynaptic machinery invol ved in mGluR7a aggregation and in modulation of glutamate neurotransmission .