The Na+/K+ ATPase is required for septate junction function and epithelial tube-size control in theDrosophilatracheal system

Abstract

Although the correct architecture of epithelial tubes is crucial for the function of organs such as the lung, kidney and vascular system, little is known about the molecular mechanisms that control tube size. We show that mutations in the ATPα α and nrv2 β subunits of the Na+/K+ ATPase cause Drosophila tracheal tubes to have increased lengths and expanded diameters. ATPαand nrv2 mutations also disrupt stable formation of septate junctions, structures with some functional and molecular similarities to vertebrate tight junctions. The Nrv2 β subunit isoforms have unique tube size and junctional functions because Nrv2, but not other DrosophilaNa+/K+ ATPase β subunits, can rescue nrv2mutant phenotypes. Mutations in known septate junctions genes cause the same tracheal tube-size defects as ATPα and nrv2 mutations,indicating that septate junctions have a previously unidentified role in epithelial tube-size control. Double mutant analyses suggest that tube-size control by septate junctions is mediated by at least two discernable pathways,although the paracellular diffusion barrier function does not appear to involved because tube-size control and diffusion barrier function are genetically separable. Together, our results demonstrate that specific isoforms of the Na+/K+ ATPase play a crucial role in septate junction function and that septate junctions have multiple distinct functions that regulate paracellular transport and epithelial tube size.

The Drosophila Claudin Kune-kune Is Required for Septate Junction Organization and Tracheal Tube Size Control

“…Since most SJ proteins show interdependence for correct localization and junction function (Behr et al 2003;Genova and Fehon 2003;Paul et al 2003;FaivreSarrailh et al 2004;Wu et al 2007), we asked whether localization of Kune depends on the presence of other SJ proteins. Indeed, Kune is mislocalized to more basal positions in the primary epithelia of mega, sinu, cor, and Atpa null mutants (Figure 2, G-J$), providing strong evidence that Kune is a SJ protein.…”

“…Kune is required for tracheal tube size control: Since almost all characterized SJ proteins are required for tracheal tube size control (Behr et al 2003;Paul et al 2003;Faivre-Sarrailh et al 2004;Llimargas et al 2004;Hijazi et al 2009;Wu et al 2007), we examined the tracheal system of kune embryos.…”

“…In Drosophila, primary (ectodermally derived) epithelia lack discernable TJs and instead use pleated septate junctions (SJ) for the paracellular barrier (Baumgartner et al 1996;Lamb et al 1998;Genova and Fehon 2003;Paul et al 2003). However, despite sharing a common barrier function, vertebrate TJs and invertebrate SJs differ in several ways.…”

Disrupted axo-glial junctions result in accumulation of abnormal mitochondria at nodes of Ranvier

“…It should be noted that Na + /K + -ATPase is a component of septate junctions in Drosophila and is required for their function (Genova and Fehon, 2003;Paul et al, 2003) and that Na + / K + -ATPase subunits have recently been detected by mass spectroscopy in paranodal membrane preparations (Ogawa et al, 2006). However, it is not yet known whether Na + /K + -ATPase plays a role in the function of paranodal junctions.…”

A mutation in the zebrafish Na,K‐ATPase subunit atp1a1a.1 provides genetic evidence that the sodium potassium pump contributes to left‐right asymmetry downstream or in parallel to nodal flow

“…It is also possible that Na,K-ATPase contributes to LR patterning by mechanisms independent of its ion pump activities. In Drosophila, it has been shown that Na,KATPase is required for septate junction formation and epithelial tube-size control in the tracheal system (Paul et al, 2003). Other ion pumps have previously been demonstrated to contribute as plasma membrane scaffolds in the assembly of signaling complexes (Baumgartner et al, 2004).…”