Premium
The C‐terminal C1 cassette of the N ‐methyl‐ d ‐aspartate receptor 1 subunit contains a bi‐partite nuclear localization sequence
Author(s) -
Holmes K. D.,
Mattar P.,
Marsh D. R.,
Jordan V.,
Weaver L. C.,
Dekaban G. A.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.00865.x
Subject(s) - protein subunit , terminal (telecommunication) , sequence (biology) , receptor , chemistry , stereochemistry , microbiology and biotechnology , biochemistry , biology , computer science , computer network , gene
The N ‐methyl‐ d ‐aspartate receptor (NMDAR) is a multimeric transmembrane protein composed of at least two subunits. One subunit, NR1, is derived from a single gene and can be subdivided into three regions: the N‐terminal extracellular domain, the transmembrane regions, and the C‐terminal intracellular domain. The N‐terminal domain is responsible for Mg 2+ metal ion binding and channel activity, while the transmembrane domains are important for ion channel formation. The intracellular C‐terminal domain is involved in regulating receptor activity and subcellular localization. Our recent experiments indicated that the intracellular C‐terminal domain, when expressed independently, localizes almost exclusively in the nucleus. An examination of the amino acid sequence reveals the presence of a putative nuclear localization sequence (NLS) in the C1 cassette of the NR1 intracellular C‐terminus. Using an expression vector designed to test whether a putative NLS sequence is a valid, functional NLS, we have demonstrated that a bi‐partite NLS does in fact exist within the NR1‐1 C‐terminus. Computer algorithms identified a putative helix–loop–helix motif that spanned the C0C1 cassettes of the C‐terminus. These data suggest that the NR1 subunit may represent another member of a family of transmembrane proteins that undergo intramembrane proteolysis, releasing a cytosolic peptide that is actively translocated to the nucleus leading to alterations in gene regulation.