Distinct LIN-10 domains are required for its neuronal function, its epithelial function, and its synaptic localization

• Published in: Molecular biology of the cell 2005-03, Vol.16 (3), p.1417-1426
• Main Authors: Glodowski, Doreen R, Wright, Tricia, Martinowich, Keri, Chang, Howard Chia-Hao, Beach, Douglas, Rongo, Christopher
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Cadherins - chemistry; Caenorhabditis elegans; Caenorhabditis elegans Proteins - chemistry; Caenorhabditis elegans Proteins - metabolism; Caenorhabditis elegans Proteins - physiology; Carrier Proteins - chemistry; Cell Lineage; Dendrites - metabolism; DNA - metabolism; DNA, Complementary - metabolism; Epithelium - metabolism; Female; Golgi Apparatus - metabolism; Immunoprecipitation; Luminescent Proteins - metabolism; Membrane Proteins - chemistry; Membrane Proteins - physiology; Microscopy, Fluorescence; Models, Biological; Molecular Sequence Data; Multigene Family; Mutation; Nerve Tissue Proteins - chemistry; Neuronal Plasticity; Neurons - metabolism; Protein Structure, Tertiary; Protein Transport; Receptors, AMPA - metabolism; Receptors, Glutamate - chemistry; Red Fluorescent Protein; Sequence Homology, Amino Acid; Synapses - metabolism; Transgenes; Vulva - metabolism
• ISSN: 1059-1524; 1939-4586; 1059-1524
• DOI: 10.1091/mbc.e04-10-0885

alpha-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors (AMPARs) mediate excitatory neurotransmission at neuronal synapses, and their regulated localization plays a role in synaptic plasticity. In Caenorhabditis 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 carboxyl-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. 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.