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First published online December 12, 2006
doi: 10.1242/10.1242/dev.02710
1 Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern
University, Evanston, IL 60208, USA.
2 Laboratory of Genetics, University of Wisconsin, Madison, WI 53706, USA.
3 Department of Pharmacology and Pittsburgh Institute for Neurodegenerative
Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260,
USA.
* Author for correspondence (e-mail: beitel{at}northwestern.edu)
Accepted 23 October 2006
The heterodimeric Na,K-ATPase has been implicated in vertebrate and
invertebrate epithelial cell junctions, morphogenesis and oncogenesis, but the
mechanisms involved are unclear. We previously showed that the
Drosophila Na,K-ATPase is required for septate junction (SJ)
formation and that of the three ß-subunit loci, only Nrv2 isoforms
support epithelial SJ barrier function and tracheal tube-size control. Here we
show that Nrv1 is endogenously co-expressed with Nrv2 in the epidermis and
tracheal system, but Nrv1 has a basolateral localization and appears to be
excluded from the Nrv2-containing SJs. When the normally neuronal Nrv3 is
expressed in epithelial cells, it does not associate with SJs. Thus, the
ß-subunit is a key determinant of Na,K-ATPase subcellular localization as
well as function. However, localization of the Na,K-ATPase to SJs is not
sufficient for junctional activity because although several Nrv2/Nrv3 chimeric
ß-subunits localize to SJs, only those containing the extracellular
domain of Nrv2 have junctional activity. Junctional activity is also specific
to different 
-subunit isoforms, with only some isoforms from the major
-subunit locus being able to provide full barrier function and produce
normal tracheal tubes. Importantly, mutations predicted to inactivate
ATP catalytic function do not compromise junctional activity,
demonstrating that the Drosophila Na,K-ATPase has an
ion-pump-independent role in junction formation and tracheal morphogenesis.
These results define new functions for the intensively studied Na,K-ATPase.
Strikingly, the rat 1 isoform has full junctional activity and can
rescue Atp-null mutants to viability, suggesting that the
Na,K-ATPase has an evolutionarily conserved role in junction formation and
function.
Key words: Na, K-ATPase, Epithelial junctions, Drosophila, Septate junctions, Trachea
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