The C-terminal C1 cassette of the N-methyl-d-aspartate receptor 1 subunit contains a bi-partite nuclear localization sequence
Version of Record online: 6 JUN 2002
Journal of Neurochemistry
Volume 81, Issue 6, pages 1152–1165, June 2002
How to Cite
Holmes, K. D., Mattar, P., Marsh, D. R., Jordan, V., Weaver, L. C. and Dekaban, G. A. (2002), The C-terminal C1 cassette of the N-methyl-d-aspartate receptor 1 subunit contains a bi-partite nuclear localization sequence. Journal of Neurochemistry, 81: 1152–1165. doi: 10.1046/j.1471-4159.2002.00865.x
- Issue online: 6 JUN 2002
- Version of Record online: 6 JUN 2002
- Resubmitted manuscript received February 1, 2002; accepted February 1, 2002.
- NMDA receptor, nuclear localization, splice variant.
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 Mg2+ 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.