Am J Physiol Cell Physiol AJP: Regulatory, Integrative and Comparative Physiology
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Am J Physiol Cell Physiol (September 21, 2001). doi:10.1152/ajpcell.00249.2001
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Articles in PresS, published online ahead of print September 21, 2001
Am J Physiol Cell Physiol, 10.1152/ajpcell.00249.2001
Submitted on June 5, 2001
Accepted on September 13, 2001

Basolateral Membrane Expression of the Kir 2.3 Channel is Coordinated by A PDZ Interaction with the Lin-7/CASK Complex

Olav Olsen1, Hui Liu1, James B Wade1, Merot Jean2, and Paul A Welling1*

1 Physiology, University of Maryland, School of Medicine, Baltimore, MD, USA
2 Biologie Celluaire et Moleculaire, Centre d'Etudes, Saclay, France

* To whom correspondence should be addressed. E-mail: pwelling{at}umaryland.edu.

The basolateral membrane sorting determinant of an inwardly rectifying potassium channel, Kir 2.3, is comprised of a unique arrangement of trafficking motifs, containing tandem, conceivably overlapping, biosynthetic targeting and PDZ-based signals. In the present study, we elucidate a mechanism by which a PDZ interaction coordinates one step in a basolateral membrane sorting program. In contrast to apical missorting of channels lacking the entire sorting domain, deletion of the PDZ binding motif caused channels to accumulate into an endosomal compartment. Here, we identify a new human ortholog of a C. elegans PDZ protein, hLin-7b, that interacts with the C-terminal tail of Kir 2.3 in renal epithelia. hLin-7b associates with the channel as a part of a multimeric complex on the basolateral membrane similar to a basolateral membrane complex in C. elegans vulva progenitor cells. Co-expression of hLin-7b with Kir 2.3 dramatically increases channel activity by stabilizing plasma membrane expression. The discovery identifies one component of the sorting machinery and provides evidence for a retention mechanism in a hierarchical basolateral trafficking program.




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