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

Vol. 17, Issue 10, 4200-4211, October 2006

This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: E06-02-0129v1 17/10/4200    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal 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 Google Scholar Google Scholar Articles by Alewine, C. Articles by Welling, P. A. Search for Related Content PubMed PubMed Citation Articles by Alewine, C. Articles by Welling, P. A.

TIP-1 Has PDZ Scaffold Antagonist Activity

Department of Physiology, University of Maryland, School of Medicine, Baltimore, MD 21201

Submitted February 13, 2006; Revised June 20, 2006; Accepted July 6, 2006
Monitoring Editor: Keith Mostov

PDZ proteins usually contain multiple protein–protein interaction domains and act as molecular scaffolds that are important for the generation and maintenance of cell polarity and cell signaling. Here, we identify and characterize TIP-1 as an atypical PDZ protein that is composed almost entirely of a single PDZ domain and functions as a negative regulator of PDZ-based scaffolding. We found that TIP-1 competes with the basolateral membrane mLin-7/CASK complex for interaction with the potassium channel Kir 2.3 in model renal epithelia. Consequently, polarized plasma membrane expression of Kir 2.3 is disrupted resulting in pronounced endosomal targeting of the channel, similar to the phenotype observed for mutant Kir 2.3 channels lacking the PDZ-binding motif. TIP-1 is ubiquitously expressed, raising the possibility that TIP-1 may play a similar role in regulating the expression of other membrane proteins containing a type I PDZ ligand.

This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E06-02-0129) on July 19, 2006.

* These authors contributed equally to this work.

Address correspondence to: Paul A. Welling (pwelling{at}umaryland.edu)

Abbreviations used: bHLH, basis helix-loop-helix; DPBS-M, Dulbecco's phosphate-buffered saline with 1 mM MgCl₂; DPC, dystrophin-associated protein complex; mGluR, metabotropic glutamate receptor; mLin-7, mammalian Lin-7; TIP-1, Tax Interacting Protein-1.

This article has been cited by other articles:

				A. K. Mason, B. E. Jacobs, and P. A. Welling AP-2-dependent Internalization of Potassium Channel Kir2.3 Is Driven by a Novel Di-hydrophobic Signal J. Biol. Chem., March 7, 2008; 283(10): 5973 - 5984. [Abstract] [Full Text] [PDF]

				C. Alewine, B.-y. Kim, V. Hegde, and P. A. Welling Lin-7 targets the Kir 2.3 channel on the basolateral membrane via a L27 domain interaction with CASK Am J Physiol Cell Physiol, December 1, 2007; 293(6): C1733 - C1741. [Abstract] [Full Text] [PDF]

				Z. Yi, R. S. Petralia, Z. Fu, C. C. Swanwick, Y.-X. Wang, K. Prybylowski, N. Sans, S. Vicini, and R. J. Wenthold The Role of the PDZ Protein GIPC in Regulating NMDA Receptor Trafficking J. Neurosci., October 24, 2007; 27(43): 11663 - 11675. [Abstract] [Full Text] [PDF]