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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, July 23, 2003, 23(16):6608-6616

This Article Full Text Full Text (PDF) 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 ISI 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 ISI Web of Science (45) Citing Articles via Google Scholar Google Scholar Articles by Ren, Z. Articles by Marshall, J. Search for Related Content PubMed PubMed Citation Articles by Ren, Z. Articles by Marshall, J.

 Previous Article  |  Next Article 

Multiple Trafficking Signals Regulate Kainate Receptor KA2 Subunit Surface Expression

Zhao Ren,¹ Nathan J. Riley,¹ Elizabeth P. Garcia,¹ James M. Sanders,² Geoffrey T. Swanson,² and John Marshall¹

¹Departments of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, Rhode Island 02912, and ²Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas 77555

The kainate receptor subunit KA2 does not form functional homomeric channels despite its structural similarity to the functional glutamate receptor 5-7subunits and high agonist binding affinity in in vitro assays. In this study, we first demonstrate that homomeric KA2 receptors fail to reach the plasma membrane and then identify the molecular mechanisms preventing surface expression. Specifically, we show that KA2 subunits form homooligomeric receptors that are confined to the endoplasmic reticulum (ER). We then demonstrate that, in both heterologous expression systems and primary neurons, the intracellular retention of KA2 is not caused by subunit misfolding but, rather, is mediated through discrete protein trafficking signals, including an arginine-rich ER retention/retrieval motif and a di-leucine endocytic sequence in the C terminus of the KA2 subunit. Disruption of these motifs results in ER exit and surface expression of KA2 homomeric receptors that remain nonfunctional. Furthermore, our data suggest that the ER retention/retrieval signal in KA2 is sterically shielded during heteromeric assembly, allowing delivery of functional heteromeric receptors to the plasma membrane. Taken together, our results illustrate novel regulatory mechanisms that control the intracellular trafficking and surface expression of kainate receptors.

Key words: kainate receptors; KA2 subunit; intracellular trafficking; ER retention; arginine-rich motif; di-leucine motif; heteromeric assembly

---

Received Mar. 21, 2003; revised May. 15, 2003; accepted May. 19, 2003.

This article has been cited by other articles:

				A. Barberis, S. Sachidhanandam, and C. Mulle GluR6/KA2 Kainate Receptors Mediate Slow-Deactivating Currents J. Neurosci., June 18, 2008; 28(25): 6402 - 6406. [Abstract] [Full Text] [PDF]

				C. Villmann and C.-M. Becker On the Hypes and Falls in Neuroprotection: Targeting the NMDA Receptor Neuroscientist, December 1, 2007; 13(6): 594 - 615. [Abstract] [PDF]

				J. J. Yi and M. D. Ehlers Emerging Roles for Ubiquitin and Protein Degradation in Neuronal Function Pharmacol. Rev., March 1, 2007; 59(1): 14 - 39. [Abstract] [Full Text] [PDF]

				G. D. Salinas, L. A. C. Blair, L. A. Needleman, J. D. Gonzales, Y. Chen, M. Li, J. D. Singer, and J. Marshall Actinfilin Is a Cul3 Substrate Adaptor, Linking GluR6 Kainate Receptor Subunits to the Ubiquitin-Proteasome Pathway J. Biol. Chem., December 29, 2006; 281(52): 40164 - 40173. [Abstract] [Full Text] [PDF]

				D. Bao, Z. Pang, M. A. Morgan, J. Parris, Y. Rong, L. Li, and J. I. Morgan Cbln1 Is Essential for Interaction-Dependent Secretion of Cbln3 Mol. Cell. Biol., December 15, 2006; 26(24): 9327 - 9337. [Abstract] [Full Text] [PDF]

				S. K. Coleman, T. Moykkynen, C. Cai, L. von Ossowski, E. Kuismanen, E. R. Korpi, and K. Keinanen Isoform-Specific Early Trafficking of AMPA Receptor Flip and Flop Variants J. Neurosci., October 25, 2006; 26(43): 11220 - 11229. [Abstract] [Full Text] [PDF]

				Y. Nasu-Nishimura, D. Hurtado, S. Braud, T. T.-T. Tang, J. T. R. Isaac, and K. W. Roche Identification of an Endoplasmic Reticulum-Retention Motif in an Intracellular Loop of the Kainate Receptor Subunit KA2 J. Neurosci., June 28, 2006; 26(26): 7014 - 7021. [Abstract] [Full Text] [PDF]

				P. Vivithanaporn, S. Yan, and G. T. Swanson Intracellular Trafficking of KA2 Kainate Receptors Mediated by Interactions with Coatomer Protein Complex I (COPI) and 14-3-3 Chaperone Systems J. Biol. Chem., June 2, 2006; 281(22): 15475 - 15484. [Abstract] [Full Text] [PDF]

				M. W. Fleck Glutamate Receptors and Endoplasmic Reticulum Quality Control: Looking beneath the Surface Neuroscientist, June 1, 2006; 12(3): 232 - 244. [Abstract] [PDF]

				D. M. Cauvi, X. Tian, K. von Loehneysen, and M. W. Robertson Transport of the IgE Receptor {alpha}-Chain Is Controlled by a Multicomponent Intracellular Retention Signal J. Biol. Chem., April 14, 2006; 281(15): 10448 - 10460. [Abstract] [Full Text] [PDF]

				J. Li, S. Zhu, X. Song, Y. Shen, H. Chen, J. Yu, K. Yi, Y. Liu, V. J. Karplus, P. Wu, et al. A Rice Glutamate Receptor-Like Gene Is Critical for the Division and Survival of Individual Cells in the Root Apical Meristem PLANT CELL, February 1, 2006; 18(2): 340 - 349. [Abstract] [Full Text] [PDF]

				X.-Q. Ren, S.-B. Cheng, M. W. Treuil, J. Mukherjee, J. Rao, K. H. Braunewell, J. M. Lindstrom, and R. Anand Structural Determinants of {alpha}4{beta}2 Nicotinic Acetylcholine Receptor Trafficking J. Neurosci., July 13, 2005; 25(28): 6676 - 6686. [Abstract] [Full Text] [PDF]

				F. Jaskolski, E. Normand, C. Mulle, and F. Coussen Differential Trafficking of GluR7 Kainate Receptor Subunit Splice Variants J. Biol. Chem., June 17, 2005; 280(24): 22968 - 22976. [Abstract] [Full Text] [PDF]

				D. A. Dodd, B. Niederoest, S. Bloechlinger, L. Dupuis, J.-P. Loeffler, and M. E. Schwab Nogo-A, -B, and -C Are Found on the Cell Surface and Interact Together in Many Different Cell Types J. Biol. Chem., April 1, 2005; 280(13): 12494 - 12502. [Abstract] [Full Text] [PDF]

				L. Valluru, J. Xu, Y. Zhu, S. Yan, A. Contractor, and G. T. Swanson Ligand Binding Is a Critical Requirement for Plasma Membrane Expression of Heteromeric Kainate Receptors J. Biol. Chem., February 18, 2005; 280(7): 6085 - 6093. [Abstract] [Full Text] [PDF]

				L. J. Druhan, J. Ai, P. Massullo, T. Kindwall-Keller, M. A. Ranalli, and B. R. Avalos Novel mechanism of G-CSF refractoriness in patients with severe congenital neutropenia Blood, January 15, 2005; 105(2): 584 - 591. [Abstract] [Full Text] [PDF]

				C. Heine, B. Koch, S. Storch, A. Kohlschutter, D. N. Palmer, and T. Braulke Defective Endoplasmic Reticulum-resident Membrane Protein CLN6 Affects Lysosomal Degradation of Endocytosed Arylsulfatase A J. Biol. Chem., May 21, 2004; 279(21): 22347 - 22352. [Abstract] [Full Text] [PDF]

				F. Jaskolski, F. Coussen, N. Nagarajan, E. Normand, C. Rosenmund, and C. Mulle Subunit Composition and Alternative Splicing Regulate Membrane Delivery of Kainate Receptors J. Neurosci., March 10, 2004; 24(10): 2506 - 2515. [Abstract] [Full Text] [PDF]

				S. Yan, J. M. Sanders, J. Xu, Y. Zhu, A. Contractor, and G. T. Swanson A C-Terminal Determinant of GluR6 Kainate Receptor Trafficking J. Neurosci., January 21, 2004; 24(3): 679 - 691. [Abstract] [Full Text] [PDF]

				Z. Ren, N. J. Riley, L. A. Needleman, J. M. Sanders, G. T. Swanson, and J. Marshall Cell Surface Expression of GluR5 Kainate Receptors Is Regulated by an Endoplasmic Reticulum Retention Signal J. Biol. Chem., December 26, 2003; 278(52): 52700 - 52709. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help