QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, January 25, 2006, 26(4):1065-1076; doi:10.1523/JNEUROSCI.3347-05.2006

This Article Full Text Full Text (PDF) Supplemental data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (19) Citing Articles via Google Scholar Google Scholar Articles by Bradley, J. Articles by Finkbeiner, S. Search for Related Content PubMed PubMed Citation Articles by Bradley, J. Articles by Finkbeiner, S.

 Previous Article  |  Next Article 

Cellular/Molecular
Splice Variants of the NR1 Subunit Differentially Induce NMDA Receptor-Dependent Gene Expression

John Bradley,¹ Sarah R. Carter,^1,3 Vikram R. Rao,^1,4 Jun Wang,¹ and Steven Finkbeiner^1,2,3,4

¹Gladstone Institute of Neurological Disease, ²Departments of Neurology and Physiology and the ³Neuroscience and ⁴Biomedical Science Programs, University of California, San Francisco, San Francisco, California 94141

Correspondence should be addressed to Steven Finkbeiner, Gladstone Institute of Neurological Disease, 1650 Owens Street, San Francisco, CA 94158. Email: sfinkbeiner{at}gladstone.ucsf.edu

Subunits of the NMDA receptor (NMDAR) associate with many postsynaptic proteins that substantially broaden its signaling capacity. Although much work has been focused on the signaling of NR2 subunits, little is known about the role of the NR1 subunit. We set out to elucidate the role of the C terminus of the NR1 subunit in NMDAR signaling. By introducing a C-terminal deletion mutant of the NR1 subunit into cultured neurons from NR1^–/– mice, we found that the C terminus was essential for NMDAR inactivation, downstream signaling, and gene expression, but not for global increases in intracellular Ca²⁺. Therefore, whereas NMDARs can increase Ca²⁺ throughout the neuron, NMDAR-dependent signaling, both local and long range, requires coupling through the NR1 C terminus. Two major NR1 splice variants differ by the presence or absence of a C-terminal domain, C1, which is determined by alternative splicing of exon 21. Analysis of these two variants showed that removal of this domain significantly reduced the efficacy of NMDAR-induced gene expression without affecting receptor inactivation. Thus, the NR1 C terminus couples to multiple downstream signaling pathways that can be modulated selectively by RNA splicing.

Key words: NMDA receptor; NR1 subunit; alternative splicing; gene expression; calcium; CREB

---

Received Aug. 9, 2005; revised Nov. 29, 2005; accepted Nov. 30, 2005.

Correspondence should be addressed to Steven Finkbeiner, Gladstone Institute of Neurological Disease, 1650 Owens Street, San Francisco, CA 94158. Email: sfinkbeiner{at}gladstone.ucsf.edu

This article has been cited by other articles:

				S. J. Barmada, G. Skibinski, E. Korb, E. J. Rao, J. Y. Wu, and S. Finkbeiner Cytoplasmic Mislocalization of TDP-43 Is Toxic to Neurons and Enhanced by a Mutation Associated with Familial Amyotrophic Lateral Sclerosis J. Neurosci., January 13, 2010; 30(2): 639 - 649. [Abstract] [Full Text] [PDF]

				R. A. Jeffrey, T. H. Ch'ng, T. J. O'Dell, and K. C. Martin Activity-Dependent Anchoring of Importin {alpha} at the Synapse Involves Regulated Binding to the Cytoplasmic Tail of the NR1-1a Subunit of the NMDA Receptor J. Neurosci., December 16, 2009; 29(50): 15613 - 15620. [Abstract] [Full Text] [PDF]

				J.-A. Lee, Z.-Z. Tang, and D. L. Black An inducible change in Fox-1/A2BP1 splicing modulates the alternative splicing of downstream neuronal target exons Genes & Dev., October 1, 2009; 23(19): 2284 - 2293. [Abstract] [Full Text] [PDF]

				M. Horak and R. J. Wenthold Different Roles of C-terminal Cassettes in the Trafficking of Full-length NR1 Subunits to the Cell Surface J. Biol. Chem., April 10, 2009; 284(15): 9683 - 9691. [Abstract] [Full Text] [PDF]

				M. E. Schober, R. A. McKnight, X. Yu, C. W. Callaway, X. Ke, and R. H. Lane Intrauterine growth restriction due to uteroplacental insufficiency decreased white matter and altered NMDAR subunit composition in juvenile rat hippocampi Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2009; 296(3): R681 - R692. [Abstract] [Full Text] [PDF]

				R. Jurd, C. Thornton, J. Wang, K. Luong, K. Phamluong, V. Kharazia, S. L. Gibb, and D. Ron Mind Bomb-2 Is an E3 Ligase That Ubiquitinates the N-Methyl-D-aspartate Receptor NR2B Subunit in a Phosphorylation-dependent Manner J. Biol. Chem., January 4, 2008; 283(1): 301 - 310. [Abstract] [Full Text] [PDF]

				M. L. Kalev-Zylinska and M. J. During Paradoxical Facilitatory Effect of Low-Dose Alcohol Consumption on Memory Mediated by NMDA Receptors J. Neurosci., September 26, 2007; 27(39): 10456 - 10467. [Abstract] [Full Text] [PDF]

				V. A. Alvarez, D. A. Ridenour, and B. L. Sabatini Distinct Structural and Ionotropic Roles of NMDA Receptors in Controlling Spine and Synapse Stability J. Neurosci., July 11, 2007; 27(28): 7365 - 7376. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help