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A more recent version of this article appeared on March 1, 2005
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Submitted on October 8, 2004
Revised on December 10, 2004
Accepted on December 18, 2004
The Waksman Institute, Department of Genetics, Rutgers University, Piscataway, NJ 08854
Monitoring Editor: Guido Guidotti
AMPA-type glutamate receptors (AMPARs) mediate excitatory neurotransmission at neuronal synapses, and their regulated localization plays a role in synaptic plasticity. In C. elegans, the PDZ and PTB domain-containing protein LIN-10 is required both for the synaptic localization of the AMPAR subunit GLR-1 and for vulval fate induction in epithelia. Here we examine the role that different LIN-10 domains play in GLR-1 localization. We find that an amino-terminal region of LIN-10 directs LIN-10 protein localization to the Golgi and to synaptic clusters. In addition, mutations in the carboxy-terminal PDZ domains prevent LIN-10 from regulating GLR-1 localization in neurons, but do not prevent LIN-10 from functioning in the vulval epithelia. A mutation in the amino-terminus prevents the protein from functioning in the vulval epithelia, but does not prevent it from functioning to regulate GLR-1 localization in neurons. Finally, we show that human Mint2 can substitute for LIN-10 to facilitate GLR-1 localization in neurons, and that the Mint2 amino-terminus is critical for this function. Taken together, our data suggest that LIN-10 uses distinct modular domains for its functions in neurons and epithelial cells, and that during evolution its vertebrate ortholog, Mint2, has retained the ability to direct AMPAR localization in neurons.
Corresponding author.
E-mail: rongo{at}waksman.rutgers.edu