A novel sorting motif in the glutamate transporter excitatory amino acid transporter 3 directs its targeting in Madin-Darby canine kidney cells and hippocampal neurons.

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  • Author(s): Cheng C;Cheng C; Glover G; Banker G; Amara SG
  • Source:
    The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2002 Dec 15; Vol. 22 (24), pp. 10643-52.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Society for Neuroscience Country of Publication: United States NLM ID: 8102140 Publication Model: Print Cited Medium: Internet ISSN: 1529-2401 (Electronic) Linking ISSN: 02706474 NLM ISO Abbreviation: J Neurosci Subsets: MEDLINE
    • Publication Information:
      Publication: Washington, DC : Society for Neuroscience
      Original Publication: [Baltimore, Md.] : The Society, c1981-
    • Subject Terms:
      Amino Acid Transport System X-AG/*analysis ; Amino Acid Transport System X-AG/*chemistry ; Hippocampus/*chemistry ; Neurons/*chemistry ; Symporters/*analysis ; Symporters/*chemistry; Amino Acid Motifs ; Amino Acid Sequence ; Amino Acid Transport System X-AG/genetics ; Amino Acid Transport System X-AG/metabolism ; Animals ; Cell Line ; Cell Polarity ; Cells, Cultured ; Dendrites/chemistry ; Dogs ; Excitatory Amino Acid Transporter 1 ; Excitatory Amino Acid Transporter 2 ; Excitatory Amino Acid Transporter 3 ; Glutamate Plasma Membrane Transport Proteins ; Hippocampus/cytology ; Hippocampus/metabolism ; Molecular Sequence Data ; Mutation ; Neurons/metabolism ; Protein Sorting Signals ; Protein Transport ; Rats ; Symporters/genetics ; Symporters/metabolism
    • Abstract:
      The glutamate transporter excitatory amino acid transporter 3 (EAAT3) is polarized to the apical surface in epithelial cells and localized to the dendritic compartment in hippocampal neurons, where it is clustered adjacent to postsynaptic sites. In this study, we analyzed the sequences in EAAT3 that are responsible for its polarized localization in Madin-Darby canine kidney (MDCK) cells and neurons. Confocal microscopy and cell surface biotinylation assays demonstrated that deletion of the EAAT3 C terminus or replacement of the C terminus of EAAT3 with the analogous region in EAAT1 eliminated apical localization in MDCK cells. The C terminus of EAAT3 was sufficient to redirect the basolateral-preferring EAAT1 and the nonpolarized EAAT2 to the apical surface. Using alanine substitution mutants, we identified a short peptide motif in the cytoplasmic C-terminal region of EAAT3 that directs its apical localization in MDCK cells. Mutation of this sequence also impairs dendritic targeting of EAAT3 in hippocampal neurons but does not interfere with the clustering of EAAT3 on dendritic spines and filopodia. These data provide the first evidence that an identical cytoplasmic motif can direct apical targeting in epithelia and somatodendritic targeting in neurons. Moreover, our results demonstrate that the two fundamental features of the localization of EAAT3 in neurons, its restriction to the somatodendritic domain and its clustering near postsynaptic sites, are mediated by distinct molecular mechanisms.
    • References:
      Cell. 1999 Jun 25;97(7):877-87. (PMID: 10399916)
      J Neurosci. 1999 Jul 15;19(14):5823-33. (PMID: 10407023)
      Neuron. 1999 Aug;23(4):637-40. (PMID: 10482229)
      Cell. 1999 Oct 15;99(2):189-98. (PMID: 10535737)
      Mol Cell Neurosci. 2000 Jan;15(1):99-111. (PMID: 10662509)
      J Comp Neurol. 2000 Mar 13;418(3):255-69. (PMID: 10701825)
      Neuron. 2000 Mar;25(3):695-706. (PMID: 10774736)
      J Neurosci. 2000 Jun 1;20(11):RC78. (PMID: 10807936)
      J Neurosci. 2000 Jun 15;20(12):4524-34. (PMID: 10844022)
      J Neurosci. 2000 Jun 15;20(12):4545-54. (PMID: 10844024)
      Annu Rev Neurosci. 2000;23:39-71. (PMID: 10845058)
      J Biol Chem. 2001 Jan 19;276(3):2168-73. (PMID: 11036075)
      J Biol Chem. 2001 Mar 23;276(12):9133-40. (PMID: 11106656)
      Nature. 2001 Mar 1;410(6824):84-8. (PMID: 11242046)
      Mol Cell Biol. 2001 Apr;21(7):2463-6. (PMID: 11259594)
      J Cell Biol. 2001 Jun 25;153(7):1499-509. (PMID: 11425878)
      Cell Mol Life Sci. 2001 Jul;58(8):1067-84. (PMID: 11529500)
      Neuron. 2001 Aug 30;31(4):607-16. (PMID: 11545719)
      Nat Cell Biol. 2002 Feb;4(2):154-9. (PMID: 11802162)
      Cell. 1990 Jul 13;62(1):63-72. (PMID: 2163770)
      J Cell Biol. 1989 Dec;109(6 Pt 1):2817-32. (PMID: 2592406)
      Proc Natl Acad Sci U S A. 1988 Nov;85(21):8335-9. (PMID: 3054884)
      J Neurosci. 1994 Sep;14(9):5559-69. (PMID: 7521911)
      Nature. 1995 Jun 15;375(6532):599-603. (PMID: 7791878)
      J Neurosci. 1995 Mar;15(3 Pt 1):1835-53. (PMID: 7891138)
      Neuron. 1994 Sep;13(3):713-25. (PMID: 7917301)
      J Biol Chem. 1996 Mar 22;271(12):6917-24. (PMID: 8636119)
      J Cell Biol. 1996 Dec;135(6 Pt 1):1619-32. (PMID: 8978827)
      Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):4155-60. (PMID: 9108121)
      Neuroscience. 1997 Dec;81(4):1031-42. (PMID: 9330365)
      Eur J Neurosci. 1997 Sep;9(9):1902-10. (PMID: 9383213)
      Am J Physiol. 1997 Dec;273(6):F1023-9. (PMID: 9435692)
      Cereb Cortex. 1998 Mar;8(2):108-16. (PMID: 9542890)
      J Neurosci. 1998 May 15;18(10):3606-19. (PMID: 9570792)
      Neuron. 1998 May;20(5):855-67. (PMID: 9620691)
      J Cell Biol. 1998 Sep 7;142(5):1245-56. (PMID: 9732285)
      J Biol Chem. 1998 Oct 2;273(40):25616-27. (PMID: 9748227)
      Methods Enzymol. 1998;296:307-18. (PMID: 9779457)
      Neuron. 1998 Dec;21(6):1487-98. (PMID: 9883740)
    • Grant Information:
      R01 MH066179 United States MH NIMH NIH HHS; R01 NS017112 United States NS NINDS NIH HHS; NS17112 United States NS NINDS NIH HHS; R01 NS033273 United States NS NINDS NIH HHS; MH 66179 United States MH NIMH NIH HHS; NS 33273 United States NS NINDS NIH HHS
    • Accession Number:
      0 (Amino Acid Transport System X-AG)
      0 (Excitatory Amino Acid Transporter 1)
      0 (Excitatory Amino Acid Transporter 2)
      0 (Excitatory Amino Acid Transporter 3)
      0 (Glutamate Plasma Membrane Transport Proteins)
      0 (Protein Sorting Signals)
      0 (Slc1a1 protein, rat)
      0 (Slc1a2 protein, rat)
      0 (Slc1a3 protein, rat)
      0 (Symporters)
    • Publication Date:
      Date Created: 20021218 Date Completed: 20030123 Latest Revision: 20200225
    • Publication Date:
      20240829
    • Accession Number:
      PMC6758410
    • Accession Number:
      12486157