Targeted Disruption of the PDZK1 Gene by Homologous Recombination
Open Access
- 1 February 2003
- journal article
- Published by Informa UK Limited in Molecular and Cellular Biology
- Vol. 23 (4), 1175-1180
- https://doi.org/10.1128/mcb.23.4.1175-1180.2003
Abstract
Proteins containing PDZ domains are involved in a large number of biological functions, including protein scaffolding, organization of ion channels, and signal transduction. We recently identified a novel PDZ domain-containing protein, PDZK1, that is selectively expressed in normal tissues, where it is associated and colocalized with MAP17, a small 17-kDa membrane-associated protein; cMOAT, an organic anion transporter implicated in multidrug resistance; and the type IIa Na/Pi cotransporter. The protein cluster formed by PDZK1, MAP17, and cMOAT is upregulated in a significant number of human carcinomas originating in the colon, breast, lung, and kidney. In order to better define the function of PDZK1 in the protein cluster and its potential role in the organization of ion channels, we generated a PDZK1 knockout mouse. While PDZK1-deficient mice developed normally, did not display any gross phenotypic abnormalities, and were fecund, lack of PDZK1 resulted in modulation of expression of selective ion channels in the kidney, as well as increased serum cholesterol levels. However, no significant redistribution of proteins known to interact with PDZK1, such as MAP17, cMOAT, and the type IIa Na/Pi cotransporter, was observed. The absence of a more significant phenotype in PDZK1-deficient mice may be due to functional compensation by other PDZ domain-containing proteins, which could be instrumental in determining the location of interacting proteins such as ion channels and other membrane-associated proteins in defined areas of the plasma membrane.Keywords
This publication has 28 references indexed in Scilit:
- Sustained Nitric Oxide Production in Macrophages Requires the Arginine Transporter CAT2Journal of Biological Chemistry, 2001
- Contrasting Localizations of MALS/LIN-7 PDZ Proteins in Brain and Molecular Compensation in Knockout MicePublished by Elsevier BV ,2001
- Interaction of the Type IIa Na/Pi Cotransporter with PDZ ProteinsPublished by Elsevier BV ,2001
- Isolation of genes identified in mouse renal proximal tubule by comparing different gene expression profilesKidney International, 1998
- Recognition of Unique Carboxyl-Terminal Motifs by Distinct PDZ DomainsScience, 1997
- Biology of the multidrug resistance-associated protein, MRPEuropean Journal Of Cancer, 1996
- Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinasesNature, 1995
- Increased expression of the 43-kD protein disrupts acetylcholine receptor clustering in myotubesThe Journal of cell biology, 1993
- Specification of Subunit Assembly by the Hydrophilic Amino-Terminal Domain of the Shaker Potassium ChannelScience, 1992
- The discs-large tumor suppressor gene of Drosophila encodes a guanylate kinase homolog localized at septate junctionsCell, 1991