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J. Biol. Chem., Vol. 277, Issue 49, 47765-47769, December 6, 2002
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From the Trafficking of
A Novel Anterograde Trafficking Signal Present in
the N-terminal Extracellular Domain of Ionotropic Glutamate
Receptors*
§,
Department of Psychiatry and Behavioral
Sciences, Stanford University, Stanford, California 94304 and the
¶ Departments of Psychiatry and Cellular and Molecular
Pharmacology, University of California, San Francisco, California
94143
-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors
to and from the postsynaptic membrane plays an important role in
regulating transmission at excitatory synapses. AMPA receptor
subunits contain a large extracellular N-terminal domain that is
important for receptor assembly (1). To further investigate the
determinants of receptor assembly and surface expression, we have
epitope-tagged the N-terminal domain of the AMPA receptor subunit,
GluR1, and expressed it in human embryonic kidney 293 cells and
hippocampal neurons. Full-length GluR1 was readily detected on the cell
surface in both cell types. However, surface expression was profoundly
decreased by deletion or replacement of nine amino acids in the extreme
N terminus. Immunoprecipitation experiments demonstrated that the
mutant GluR1 in which this sequence was deleted still interacts with
GluR2, suggesting that mutant GluR1 is capable of at least partial
assembly into heteromeric structures. The mutant forms of GluR1
co-localize with an endoplasmic reticulum marker suggesting that they
are retained in this structure. These results suggest a specific
function of a short sequence present in the N-terminal domain in
controlling anterograde trafficking of ionotropic glutamate receptors.
*
This work was supported by grants from the National
Institutes of Health.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of
Psychiatry and Behavioral Sciences, 1201 Welch Rd., Rm. P105, Stanford University, Palo Alto, CA 94304. Tel.: 650-724-2730; Fax:
650-724-2753; E-mail: malenka@stanford.edu.
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