title: Distinct LIN-10 domains are required for its neuronal function, its epithelial function, and its synaptic localization.
abstract: 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.
authors.affiliation: The Waksman Institute, Department of Genetics, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Doreen R
authors.initials: DR
authors.lastname: Glodowski
authors.forename: Tricia
authors.initials: T
authors.lastname: Wright
authors.forename: Keri
authors.initials: K
authors.lastname: Martinowich
authors.forename: Howard Chia-Hao
authors.initials: HC
authors.lastname: Chang
authors.forename: Douglas
authors.initials: D
authors.lastname: Beach
authors.forename: Christopher
authors.initials: C
authors.lastname: Rongo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015820:Cadherins / Q000737:chemistry; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D002352:Carrier Proteins / Q000737:chemistry; D019070:Cell Lineage; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism*; D005260:Female; D006056:Golgi Apparatus / Q000378:metabolism; D047468:Immunoprecipitation; D008164:Luminescent Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D018091:Receptors, AMPA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D013569:Synapses / Q000378:metabolism*; D019076:Transgenes; D014844:Vulva / Q000378:metabolism; D000097573:Red Fluorescent Protein
chemical_list: D015820:Cadherins; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D004247:DNA; D018076:DNA, Complementary; D008164:Luminescent Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D000097573:Red Fluorescent Protein; C491636:APBA2 protein, human; C492973:alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype glutamate receptor, human; C096470:glr-1 protein, C elegans; C064105:lin-10 protein, C elegans