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Published online
doi:10.1083/jcb.200606116
The Journal of Cell Biology, Vol. 176, No. 2, 223-230
The Rockefeller University Press, 0021-9525 $30.00
© Cibrián-Uhalte et al.
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Article

Involvement of zebrafish Na+,K+ ATPase in myocardial cell junction maintenance



Elena Cibrián-Uhalte1, Adam Langenbacher2, Xiaodong Shu2, Jau-Nian Chen2,3,4, and Salim Abdelilah-Seyfried1

1 Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany
2 Department of Molecular, Cell, and Developmental Biology, 3 Jonsson Comprehensive Cancer Center, and 4 Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095

Correspondence to Salim Abdelilah-Seyfried: salim{at}mdc-berlin.de; or Jau-Nian Chen: chenjn{at}mcdb.ucla.edu

Na+,K+ ATPase is an essential ion pump involved in regulating ionic concentrations within epithelial cells. The zebrafish heart and mind (had) mutation, which disrupts the {alpha}1B1 subunit of Na+,K+ ATPase, causes heart tube elongation defects and other developmental abnormalities that are reminiscent of several epithelial cell polarity mutants, including nagie oko (nok). We demonstrate genetic interactions between had and nok in maintaining Zonula occludens-1 (ZO-1)–positive junction belts within myocardial cells. Functional tests and pharmacological inhibition experiments demonstrate that Na+,K+ ATPase activity is positively regulated via an N-terminal phosphorylation site that is necessary for correct heart morphogenesis to occur, and that maintenance of ZO-1 junction belts requires ion pump activity. These findings suggest that the correct ionic balance of myocardial cells is essential for the maintenance of epithelial integrity during heart morphogenesis.

Abbreviations used in this paper: cmlc2, cardiac myosin light chain 2; hpf, hours postfertilization; Had, heart and mind; Has, heart and soul; MO, morpholino antisense oligonucleotide; Nok, Nagie oko; wt, wild type; ZO-1, Zonula occludens-1.


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