JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on November 27, 2002
This Article
Right arrow Full Text (Accepted Manuscript)
Right arrow All Versions of this Article:
277/49/46891    most recent
M205274200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Koshimizu, T.-a.
Right arrow Articles by Tsujimoto, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Koshimizu, T.-a.
Right arrow Articles by Tsujimoto, G.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Papers In Press, published online ahead of print October 1, 2002
J. Biol. Chem, 10.1074/jbc.M205274200
Submitted on May 29, 2002
Revised on September 16, 2002
Accepted on October 1, 2002

Heteromultimerization modulates P2X receptor-functions through participating extracellular and C-terminal subdomains

Taka-aki Koshimizu, Susumu Ueno, Akito Tanoue, Nobuyuki Yanagihara, Stanko S. Stojilkovic, and Gozoh Tsujimoto

Department of Molecular, Cell Pharmacology, National Center for Child Health and Development Research Institute, Tokyo 154-8567

Corresponding Author: gtsujimoto{at}nch.go.jp

P2X purinergic receptors (P2XRs) differ among themselves with respect to their ligand preferences and channel kinetics during activation, desensitization and recovery. However, the contributions of distinct receptor subdomains to the subtype-specific behavior have been incompletely characterized. Here, we show that homomeric receptors having the extracellular domain of P2X3 subunit in the P2X2a-based backbone (P2X2a/X3ex) mimicked two intrinsic functions of P2X3R, sensitivity to alpha beta -methylene ATP and ecto-ATPase-dependent recovery from endogenous desensitization; these two functions were localized to N- and C-terminal halves of P2X3R extracellular loop, respectively. The chimeric P2X2aR/X3ex receptors also desensitized with accelerated rates compared to native P2X2aR, and the introduction of P2X2-C-terminal splicing into the chimeric subunit (P2X2b/X3ex) further increased the rate of desensitization. Physical and functional heteromerization of native P2X2a and P2X2b subunits was also demonstrated. In heteromeric receptors, the ectodomain of P2X3 was a structural determinant for ligand selectivity and recovery from desensitization, and the C-terminus of P2X2 was an important factor for desensitization rate. Furthermore, [gamma -32P]8-azido ATP, a photoreactive agonist, was effectively cross-linked to P2X3 subunit in homomeric receptors but not in heteromeric P2X2+P2X3Rs. These results indicate that heteromeric receptors formed by distinct P2XR subunits develop new functions resulting from integrative effects of the participating extracellular and C-terminal subdomains.


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


This article has been cited by other articles:


Home page
 Mol. Pharmacol.Home page
T.-a. Koshimizu, K. Kretschmannova, M.-L. He, S. Ueno, A. Tanoue, N. Yanagihara, S. S. Stojilkovic, and G. Tsujimoto
Carboxyl-Terminal Splicing Enhances Physical Interactions between the Cytoplasmic Tails of Purinergic P2X Receptors
Mol. Pharmacol., May 1, 2006; 69(5): 1588 - 1598.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Fabbretti, E. Sokolova, L. Masten, M. D'Arco, A. Fabbro, A. Nistri, and R. Giniatullin
Identification of Negative Residues in the P2X3 ATP Receptor Ectodomain as Structural Determinants for Desensitization and the Ca2+-sensing Modulatory Sites
J. Biol. Chem., December 17, 2004; 279(51): 53109 - 53115.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
T.-a. Koshimizu, G. Tsujimoto, A. Hirasawa, Y. Kitagawa, and A. Tanoue
Carvedilol selectively inhibits oscillatory intracellular calcium changes evoked by human {alpha}1D- and {alpha}1B-adrenergic receptors
Cardiovasc Res, September 1, 2004; 63(4): 662 - 672.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
H. Zemkova, M.-L. He, T.-a. Koshimizu, and S. S. Stojilkovic
Identification of Ectodomain Regions Contributing to Gating, Deactivation, and Resensitization of Purinergic P2X Receptors
J. Neurosci., August 4, 2004; 24(31): 6968 - 6978.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M.-L. He, A. E. Gonzalez-Iglesias, and S. S. Stojilkovic
Role of Nucleotide P2 Receptors in Calcium Signaling and Prolactin Release in Pituitary Lactotrophs
J. Biol. Chem., November 21, 2003; 278(47): 46270 - 46277.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
M.-L. He, H. Zemkova, T.-a. Koshimizu, M. Tomic, and S. S. Stojilkovic
Intracellular calcium measurements as a method in studies on activity of purinergic P2X receptor channels
Am J Physiol Cell Physiol, August 1, 2003; 285(2): C467 - C479.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M.-L. He, H. Zemkova, and S. S. Stojilkovic
Dependence of Purinergic P2X Receptor Activity on Ectodomain Structure
J. Biol. Chem., March 14, 2003; 278(12): 10182 - 10188.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.