{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T09:13:04Z","timestamp":1791105184502,"version":"4.1.0"},"reference-count":41,"publisher":"American Society for Cell Biology (ASCB)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2005,3]]},"abstract":"<jats:p>\u03b1-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.<\/jats:p>","DOI":"10.1091\/mbc.e04-10-0885","type":"journal-article","created":{"date-parts":[[2005,1,13]],"date-time":"2005-01-13T01:24:18Z","timestamp":1105579458000},"page":"1417-1426","source":"Crossref","is-referenced-by-count":23,"title":["Distinct LIN-10 Domains Are Required for Its Neuronal Function, Its Epithelial Function, and Its Synaptic Localization"],"prefix":"10.1091","volume":"16","author":[{"given":"Doreen R.","family":"Glodowski","sequence":"first","affiliation":[{"name":"The Waksman Institute, Department of Genetics, Rutgers University, Piscataway, NJ 08854"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tricia","family":"Wright","sequence":"additional","affiliation":[{"name":"The Waksman Institute, Department of Genetics, Rutgers University, Piscataway, NJ 08854"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keri","family":"Martinowich","sequence":"additional","affiliation":[{"name":"The Waksman Institute, Department of Genetics, Rutgers University, Piscataway, NJ 08854"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard Chia-Hao","family":"Chang","sequence":"additional","affiliation":[{"name":"The Waksman Institute, Department of Genetics, Rutgers University, Piscataway, NJ 08854"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Beach","sequence":"additional","affiliation":[{"name":"The Waksman Institute, Department of Genetics, Rutgers University, Piscataway, NJ 08854"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Rongo","sequence":"additional","affiliation":[{"name":"The Waksman Institute, Department of Genetics, Rutgers University, Piscataway, NJ 08854"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1076","reference":[{"key":"REF1","doi-asserted-by":"crossref","unstructured":"Biederer, T., Cao, X., Sudhof, T. C., and Liu, X. (2002). Regulation of APP-dependent transcription complexes by Mint\/X11s: differential functions of Mint isoforms.J. Neurosci.22, 7340-7351.","DOI":"10.1523\/JNEUROSCI.22-17-07340.2002"},{"key":"REF2","doi-asserted-by":"crossref","unstructured":"Biederer, T., and Sudhof, T. C. (2000). Mints as adaptors. Direct binding to neurexins and recruitment of munc18.J. Biol. Chem.275, 39803-39806.","DOI":"10.1074\/jbc.C000656200"},{"key":"REF3","doi-asserted-by":"crossref","unstructured":"Bolton, M. M., Blanpied, T. A., and Ehlers, M. D. (2000). Localization and stabilization of ionotropic glutamate receptors at synapses.Cell Mol. Life Sci.57, 1517-1525.","DOI":"10.1007\/PL00000636"},{"key":"REF4","doi-asserted-by":"crossref","unstructured":"Borg, J. P., Ooi, J., Levy, E., and Margolis, B. (1996). The phosphotyrosine interaction domains of X11 and FE65 bind to distinct sites on the YENPTY motif of amyloid precursor protein.Mol. Cell. Biol.16, 6229-6241.","DOI":"10.1128\/MCB.16.11.6229"},{"key":"REF5","doi-asserted-by":"crossref","unstructured":"Borg, J. P., Straight, S. W., Kaech, S. M., de Taddeo-Borg, M., Kroon, D. E., Karnak, D., Turner, R. S., Kim, S. K., and Margolis, B. (1998). Identification of an evolutionarily conserved heterotrimeric protein complex involved in protein targeting.J. Biol. Chem.273, 31633-31636.","DOI":"10.1074\/jbc.273.48.31633"},{"key":"REF6","doi-asserted-by":"crossref","unstructured":"Burbea, M., Dreier, L., Dittman, J. S., Grunwald, M. E., and Kaplan, J. M. (2002). Ubiquitin and AP180 regulate the abundance of GLR-1 glutamate receptors at postsynaptic elements inC. elegans.Neuron35, 107-120.","DOI":"10.1016\/S0896-6273(02)00749-3"},{"key":"REF7","doi-asserted-by":"crossref","unstructured":"Campbell, R. E., Tour, O., Palmer, A. E., Steinbach, P. A., Baird, G. S., Zacharias, D. A., and Tsien, R. Y. (2002). A monomeric red fluorescent protein.Proc. Natl. Acad. Sci. USA99, 7877-7882.","DOI":"10.1073\/pnas.082243699"},{"key":"REF8","unstructured":"Dingledine, R., Borges, K., Bowie, D., and Traynelis, S. F. (1999). The glutamate receptor ion channels.Pharmacol. Rev.51, 7-61."},{"key":"REF9","doi-asserted-by":"crossref","unstructured":"Doyle, D. A., Lee, A., Lewis, J., Kim, E., Sheng, M., and MacKinnon, R. (1996). Crystal structure of a complexed and peptide-free membrane protein-binding domain: molecular basis of peptide recognition by PDZ.Cell85, 1067-1076.","DOI":"10.1016\/S0092-8674(00)81307-0"},{"key":"REF10","doi-asserted-by":"crossref","unstructured":"Garner, C. C., Nash, J., and Huganir, R. L. (2000). PDZ domains in synapse assembly and signalling.Trends Cell Biol.10, 274-280.","DOI":"10.1016\/S0962-8924(00)01783-9"},{"key":"REF11","doi-asserted-by":"crossref","unstructured":"Gomes, A. R., Correia, S. S., Carvalho, A. L., and Duarte, C. B. (2003). Regulation of AMPA receptor activity, synaptic targeting and recycling: role in synaptic plasticity.Neurochem. Res.28, 1459-1473.","DOI":"10.1023\/A:1025610122776"},{"key":"REF12","doi-asserted-by":"crossref","unstructured":"Hata, Y., Butz, S., and Sudhof, T. C. (1996). CASK: a novel dlg\/PSD95 homolog with an N-terminal calmodulin-dependent protein kinase domain identified by interaction with neurexins.J. Neurosci.16, 2488-2494.","DOI":"10.1523\/JNEUROSCI.16-08-02488.1996"},{"key":"REF13","doi-asserted-by":"crossref","unstructured":"Hayashi, Y., Shi, S. H., Esteban, J. A., Piccini, A., Poncer, J. C., and Malinow, R. (2000). Driving AMPA receptors into synapses by LTP and CaMKII: requirement for GluR1 and PDZ domain interaction.Science287, 2262-2267.","DOI":"10.1126\/science.287.5461.2262"},{"key":"REF14","doi-asserted-by":"crossref","unstructured":"Herman, R. K., and Hedgecock, E. M. (1990). Limitation of the size of the vulval primordium ofCaenorhabditis elegansbylin-15expression in surrounding hypodermis.Nature348, 169-171.","DOI":"10.1038\/348169a0"},{"key":"REF15","doi-asserted-by":"crossref","unstructured":"Hill, K., Li, Y., Bennett, M., McKay, M., Zhu, X., Shern, J., Torre, E., Lah, J. J., Levey, A. I., and Kahn, R. A. (2003). Munc18 interacting proteins: ADP-ribosylation factor-dependent coat proteins that regulate the traffic of beta-Alzheimer's precursor protein.J. Biol. Chem.278, 36032-36040.","DOI":"10.1074\/jbc.M301632200"},{"key":"REF16","doi-asserted-by":"crossref","unstructured":"Hollmann, M., and Heinemann, S. (1994). Cloned glutamate receptors.Annu. Rev. Neurosci.17, 31-108.","DOI":"10.1146\/annurev.ne.17.030194.000335"},{"key":"REF17","doi-asserted-by":"crossref","unstructured":"Hoskins, R., Hajnal, A. F., Harp, S. A., and Kim, S. K. (1996). TheC. elegansvulval induction gene lin-2 encodes a member of the MAGUK family of cell junction proteins.Development122, 97-111.","DOI":"10.1242\/dev.122.1.97"},{"key":"REF18","doi-asserted-by":"crossref","unstructured":"Hsueh, Y. P., Yang, F. C., Kharazia, V., Naisbitt, S., Cohen, A. R., Weinberg, R. J., and Sheng, M. (1998). Direct interaction of CASK\/LIN-2 and syndecan heparan sulfate proteoglycan and their overlapping distribution in neuronal synapses.J. Cell Biol.142, 139-151.","DOI":"10.1083\/jcb.142.1.139"},{"key":"REF19","doi-asserted-by":"crossref","unstructured":"Kaech, S. M., Whitfield, C. W., and Kim, S. K. (1998). The LIN-2\/LIN-7\/LIN-10 complex mediates basolateral membrane localization of theC. elegansEGF receptor LET-23 in vulval epithelial cells.Cell94, 761-771.","DOI":"10.1016\/S0092-8674(00)81735-3"},{"key":"REF20","doi-asserted-by":"crossref","unstructured":"Kim, S. K., and Horvitz, H. R. (1990). TheCaenorhabditis elegansgenelin-10is broadly expressed while required specifically for the determination of vulval cell fates.Genes Dev.4, 357-371.","DOI":"10.1101\/gad.4.3.357"},{"key":"REF21","doi-asserted-by":"crossref","unstructured":"Lau, K. F., McLoughlin, D. M., Standen, C., and Miller, C. C. (2000). X11 alpha and x11 beta interact with presenilin-1 via their PDZ domains.Mol. Cell Neurosci.16, 557-565.","DOI":"10.1006\/mcne.2000.0898"},{"key":"REF22","doi-asserted-by":"crossref","unstructured":"Malinow, R., Mainen, Z. F., and Hayashi, Y. (2000). LTP mechanisms: from silence to four-lane traffic.Curr. Opin. Neurobiol.10, 352-357.","DOI":"10.1016\/S0959-4388(00)00099-4"},{"key":"REF23","doi-asserted-by":"crossref","unstructured":"Margolis, B. (1999). The PTB domain: the name doesn't say it all.Trends Endocrinol. Metab.10, 262-267.","DOI":"10.1016\/S1043-2760(99)00168-X"},{"key":"REF24","doi-asserted-by":"crossref","unstructured":"McLoughlin, D. M., Irving, N. G., Brownlees, J., Brion, J. P., Leroy, K., and Miller, C. C. (1999). Mint2\/X11-like colocalizes with the Alzheimer's disease amyloid precursor protein and is associated with neuritic plaques in Alzheimer's disease.Eur. J. Neurosci.11, 1988-1994.","DOI":"10.1046\/j.1460-9568.1999.00610.x"},{"key":"REF25","doi-asserted-by":"crossref","unstructured":"Morais Cabral, J. H., Petosa, C., Sutcliffe, M. J., Raza, S., Byron, O., Poy, F., Marfatia, S. M., Chishti, A. H., and Liddington, R. C. (1996). Crystal structure of a PDZ domain.Nature382, 649-652.","DOI":"10.1038\/382649a0"},{"key":"REF26","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.10.7.2343"},{"key":"REF27","doi-asserted-by":"crossref","unstructured":"Okamoto, M., Matsuyama, T., and Sugita, M. (2000). Ultrastructural localization of mint1 at synapses in mouse hippocampus.Eur. J. Neurosci.12, 3067-3072.","DOI":"10.1046\/j.1460-9568.2000.00200.x"},{"key":"REF28","doi-asserted-by":"crossref","unstructured":"Okamoto, M., and Sudhof, T. C. (1997). Mints, Munc18-interacting proteins in synaptic vesicle exocytosis.J. Biol. Chem.272, 31459-31464.","DOI":"10.1074\/jbc.272.50.31459"},{"key":"REF29","doi-asserted-by":"crossref","unstructured":"Passafaro, M., Piech, V., and Sheng, M. (2001). Subunit-specific temporal and spatial patterns of AMPA receptor exocytosis in hippocampal neurons.Nat. Neurosci.4, 917-926.","DOI":"10.1038\/nn0901-917"},{"key":"REF30","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.01-10-0514"},{"key":"REF31","doi-asserted-by":"crossref","unstructured":"Rongo, C. (2001). Disparate cell types use a shared complex of PD2 proteins for polarized protein localization.Cytokine Growth Factor Rev.12,349-359.","DOI":"10.1016\/S1359-6101(01)00011-9"},{"key":"REF32","doi-asserted-by":"crossref","unstructured":"Rongo, C., and Kaplan, J. K. (1999). CaMKII regulates the density of central glutamatergic synapses in vivo.Nature402, 195-199.","DOI":"10.1038\/46065"},{"key":"REF33","doi-asserted-by":"crossref","unstructured":"Rongo, C., Whitfield, C. W., Rodal, A., Kim, S. K., and Kaplan, J. M. (1998). LIN-10 is a shared component of the polarized protein localization pathways in neurons and epithelia.Cell94, 751-759.","DOI":"10.1016\/S0092-8674(00)81734-1"},{"key":"REF34","doi-asserted-by":"crossref","unstructured":"Setou, M., Nakagawa, T., Seog, D. H., and Hirokawa, N. (2000). Kinesin superfamily motor protein KIF17 and mLin-10 in NMDA receptor-containing vesicle transport.Science288, 1796-1802.","DOI":"10.1126\/science.288.5472.1796"},{"key":"REF35","doi-asserted-by":"crossref","unstructured":"Shi, S., Hayashi, Y., Esteban, J. A., and Malinow, R. (2001). Subunit-specific rules governing AMPA receptor trafficking to synapses in hippocampal pyramidal neurons.Cell105, 331-343.","DOI":"10.1016\/S0092-8674(01)00321-X"},{"key":"REF36","doi-asserted-by":"crossref","unstructured":"Shi, S. H., Hayashi, Y., Petralia, R. S., Zaman, S. H., Wenthold, R. J., Svoboda, K., and Malinow, R. (1999). Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation.Science284, 1811-1816.","DOI":"10.1126\/science.284.5421.1811"},{"key":"REF37","doi-asserted-by":"crossref","unstructured":"Simske, J. S., Kaech, S. M., Harp, S. A., and Kim, S. K. (1996). LET-23 receptor localization by the cell junction protein LIN-7 duringC. elegansvulval induction.Cell85, 195-204.","DOI":"10.1016\/S0092-8674(00)81096-X"},{"key":"REF38","doi-asserted-by":"crossref","unstructured":"Stricker, N. L., and Huganir, R. L. (2003). The PDZ domains of mLin-10 regulate its trans-Golgi network targeting and the surface expression of AMPA receptors.Neuropharmacology45, 837-848.","DOI":"10.1016\/S0028-3908(03)00275-2"},{"key":"REF39","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.10.6.2087"},{"key":"REF40","unstructured":"Wood, W. B. (1988). The NematodeC. elegans, Cold Spring Harbor, NY: Cold Spring Harbor Laboratory."},{"key":"REF41","doi-asserted-by":"crossref","unstructured":"Yandell, M. D., Edgar, L. G., and Wood, W. B. (1994). Trimethylpsoralen induces small deletion mutations inCaenorhabditis elegans.Proc. Natl. Acad. Sci. USA91, 1381-1385.","DOI":"10.1073\/pnas.91.4.1381"}],"container-title":["Molecular Biology of the Cell"],"original-title":[],"language":"en","deposited":{"date-parts":[[2021,7,3]],"date-time":"2021-07-03T23:36:19Z","timestamp":1625355379000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.molbiolcell.org\/doi\/10.1091\/mbc.e04-10-0885"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,3]]},"references-count":41,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2005,3]]}},"alternative-id":["10.1091\/mbc.e04-10-0885"],"URL":"https:\/\/doi.org\/10.1091\/mbc.e04-10-0885","relation":{},"ISSN":["1059-1524","1939-4586"],"issn-type":[{"value":"1059-1524","type":"print"},{"value":"1939-4586","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,3]]}}}