The cell adhesion molecule Fasciclin2 regulates brush border length and organization in Drosophila renal tubules

Abstract

Multicellular organisms rely on cell adhesion molecules to coordinate cell–cell interactions, and to provide navigational cues during tissue formation. In Drosophila, Fasciclin 2 (Fas2) has been intensively studied due to its role in nervous system development and maintenance; yet, Fas2 is most abundantly expressed in the adult renal (Malpighian) tubule rather than in neuronal tissues. The role Fas2 serves in this epithelium is unknown. Here we show that Fas2 is essential to brush border maintenance in renal tubules of Drosophila. Fas2 is dynamically expressed during tubule morphogenesis, localizing to the brush border whenever the tissue is transport competent. Genetic manipulations of Fas2 expression levels impact on both microvilli length and organization, which in turn dramatically affect stimulated rates of fluid secretion by the tissue. Consequently, we demonstrate a radically different role for this well-known cell adhesion molecule, and propose that Fas2-mediated intermicrovillar homophilic adhesion complexes help stabilize the brush border.

When two cells are better than one: specialized stellate cells provide a privileged route for uniquely rapid water flux inDrosophilarenal tubule

“…The complex polyglucan, dextran, can be readily fluorescently labelled, and also can be size-selected to ranges that can be swept along by water flux, but then trapped in a pathway of restricted permeability. Both the principal and stellate cells have apical microvilli, which in principal cells are stabilised by Fas2 (40) and contain mitochondria to support intense activity of the V-ATPase (41); and both cell types also possess basal infoldings, that increase the available surface area for transport (42). We thus stimulated tubules in the presence of fluorescently-labelled dextran, which pilot experiments had shown was too large to move across the epithelium.…”

“…7 ). The main, principal cell has long apical microvilli (40), each containing a mitochondrion (41), and loaded with proton-pumping V-ATPase and is thought to drive an exchanger from the NHA family to produce a net K + flux. Basolaterally, the infoldings contain high levels of Na + , K + -ATPase (46), inward rectifier K + channels (10, 11), and Na + /K + /Cl − cotransporters (14).…”

An Axon-Pathfinding Mechanism Preserves Epithelial Tissue Integrity

“…Five of these have transmembrane domains, and 9 are considered to be neuronal 37 . The other two, which have been studied in non-neuronal cells in the trachea, Malpighian (renal) tubule, and in glial cells, are tethered to the membrane by glycosylphosphatidylinositol (GPI) anchors, indicating that they have only adhesive function 5,[37][38][39] . Since the FE is not neuronal, these observations suggest the possibility that Fas2 might mediate epithelial cell reintegration through adhesion alone.…”

“…Fas2 G0336 tissue, consistent with the finding that Nrg rescues both these mutants (Figures 2A and 4A). UAS-Fas2-Extracellular, which includes the extracellular and transmembrane regions but lacks an intracellular domain, rescues a non-neuronal function of Fas2, namely the regulation of brush border length in the Malpighian tubule epithelium 38 . However, we found that neither UAS-Fas2-Extracellular nor UAS-Fas2-Intracellular (the transmembrane and intracellular region of isoform PD) rescue reintegration failure in Fas2 G0336 tissue, though both variants localize at lateral cell junctions ( Fig 4A,B).…”

Identification of the septate junction protein gliotactin in the mosquito, Aedes aegypti: evidence for a role in increased paracellular permeability in larvae

“…In D. melanogaster, Gli is also required for parallel alignment of wing hairs in the adult wing epithelium, and this Gli function is dependent on its localization to the apical cell membranes (Venema et al, 2004). Evidence for a non-junctional role for SJ proteins also comes from a finding that a cell adhesion molecule Fasciclin 2 (Fas2), which is known to localize to SJs in the Malpighian tubules of late-stage D. melanogaster embryos, switches its localization to the apical membrane of the principal cells in larval and adult flies where it elicits effects on microvillus length and organization as well as tubule transport capacity (Halberg et al, 2016).…”