HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 32, 29169-29175, August 12, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/32/29169    most recent M501301200v1 Submit a Letter to Editor 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 PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Qi, A.-D. Articles by Nicholas, R. A. Search for Related Content PubMed PubMed Citation Articles by Qi, A.-D. Articles by Nicholas, R. A. Social Bookmarking                      What's this?

The Apical Targeting Signal of the P2Y₂ Receptor Is Located in Its First Extracellular Loop^*

Ai-Dong Qi, Samuel C. Wolff, and Robert A. Nicholas

From the Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7365

P2Y₂ and P2Y₄ receptors, which have 52% sequence identity, are both expressed at the apical membrane of Madin-Darby canine kidney cells, but the locations of their apical targeting signals are distinctly different. The targeting signal of the P2Y₂ receptor is located between the N terminus and 7TM, whereas that of the P2Y₄ receptor is present in its C-terminal tail. To identify the apical targeting signal in the P2Y₂ receptor, regions of the P2Y₂ receptor were progressively substituted with the corresponding regions of the P2Y₄ receptor lacking its targeting signal. Characterization of these chimeras and subsequent mutational analysis revealed that four amino acids (Arg⁹⁵, Gly⁹⁶, Asp⁹⁷, and Leu¹⁰⁸) in the first extracellular loop play a major role in apical targeting of the P2Y₂ receptor. Mutation of RGD to RGE had no effect on P2Y₂ receptor targeting, indicating that receptor-integrin interactions are not involved in apical targeting. P2Y₂ receptor mutants were localized in a similar manner in Caco-2 colon epithelial cells. This is the first identification of an extracellular protein-based targeting signal in a seven-transmembrane receptor.

Received for publication, February 3, 2005 , and in revised form, May 19, 2005.

^* This work was supported by National Institutes of Health Grant R01 HL71131 (to R. A. N.). The costs of publication of this article were defrayed in part by the payment of page charges. This 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 Pharmacology, The University of North Carolina at Chapel Hill, CB 7365, Chapel Hill, NC 27599-7365. Tel.: 919-966-6547; Fax: 919-966-5640; E-mail: nicholas{at}med.unc.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				O. J. Baker, J. M. Camden, R. S. Redman, J. E. Jones, C. I. Seye, L. Erb, and G. A. Weisman Proinflammatory cytokines tumor necrosis factor-{alpha} and interferon-{gamma} alter tight junction structure and function in the rat parotid gland Par-C10 cell line Am J Physiol Cell Physiol, November 1, 2008; 295(5): C1191 - C1201. [Abstract] [Full Text] [PDF]

				Z. Liao, C. I. Seye, G. A. Weisman, and L. Erb The P2Y2 nucleotide receptor requires interaction with {alpha}v integrins to access and activate G12 J. Cell Sci., May 1, 2007; 120(9): 1654 - 1662. [Abstract] [Full Text] [PDF]

				O. A. Akimova, A. Grygorczyk, R. A. Bundey, N. Bourcier, M. Gekle, P. A. Insel, and S. N. Orlov Transient Activation and Delayed Inhibition of Na+,K+,Cl- Cotransport in ATP-treated C11-MDCK Cells Involve Distinct P2Y Receptor Subtypes and Signaling Mechanisms J. Biol. Chem., October 20, 2006; 281(42): 31317 - 31325. [Abstract] [Full Text] [PDF]

				M. P. Abbracchio, G. Burnstock, J.-M. Boeynaems, E. A. Barnard, J. L. Boyer, C. Kennedy, G. E. Knight, M. Fumagalli, C. Gachet, K. A. Jacobson, et al. International Union of Pharmacology LVIII: Update on the P2Y G Protein-Coupled Nucleotide Receptors: From Molecular Mechanisms and Pathophysiology to Therapy Pharmacol. Rev., September 1, 2006; 58(3): 281 - 341. [Abstract] [Full Text] [PDF]

				M. Grati, N. Aggarwal, E. E. Strehler, and R. J. Wenthold Molecular determinants for differential membrane trafficking of PMCA1 and PMCA2 in mammalian hair cells J. Cell Sci., July 15, 2006; 119(14): 2995 - 3007. [Abstract] [Full Text] [PDF]

				S. Bagchi, Z. Liao, F. A. Gonzalez, N. E. Chorna, C. I. Seye, G. A. Weisman, and L. Erb The P2Y2 Nucleotide Receptor Interacts with {alpha}v Integrins to Activate Go and Induce Cell Migration J. Biol. Chem., November 25, 2005; 280(47): 39050 - 39057. [Abstract] [Full Text] [PDF]