Drosophila Rab23 Is Involved in the Regulation of the Number and Planar Polarization of the Adult Cuticular Hairs

Abstract

The planar coordination of cellular polarization is an important, yet not well-understood aspect of animal development. In a screen for genes regulating planar cell polarization in Drosophila, we identified Rab23, encoding a putative vesicular trafficking protein. Mutations in the Drosophila Rab23 ortholog result in abnormal trichome orientation and the formation of multiple hairs on the wing, leg, and abdomen. We show that Rab23 is required for hexagonal packing of the wing cells. We found that Rab23 is able to associate with the proximally accumulated Prickle protein, although Rab23 itself does not seem to display a polarized subcellular distribution in wing cells, and it appears to play a relatively subtle role in cortical polarization of the polarity proteins. The absence of Rab23 leads to increased actin accumulation in the subapical region of the pupal wing cells that fail to restrict prehair initiation to a single site. Rab23 acts as a dominant enhancer of the weak multiple hair phenotype exhibited by the core polarity mutations, whereas the Rab23 homozygous mutant phenotype is sensitive to the gene dose of the planar polarity effector genes. Together, our data suggest that Rab23 contributes to the mechanism that inhibits hair formation at positions outside of the distal vertex by activating the planar polarity effector system.

Mink1 Regulates β-Catenin-Independent Wnt Signaling via Prickle Phosphorylation

“…Adding to this mechanism, Rab5 was implicated for the endocytic trafficking and apical localization of Fmi and the establishment of PCP in the Drosophila wing (32), as well as for the localization of E-cadherin during zebrafish gastrulation (52). Another Rab protein, Rab23, was identified in a screen for genes affecting PCP in the fly wing (38). Recent findings obtained in Drosophila have further established that endocytic trafficking contributes to stably localizing Fmi to junctions, and that the clustering of PCP complexes into puncta depends on the recruitment of the cytoplasmic components Dsh and Pk (47).…”

“…Rab5 specifically and endosomal trafficking in general have previously been linked to the establishment of PCP in Drosophila (11,21,32,42,46) and to the regulation of Wnt11-and E-cadherin-dependent cell cohesion during zebrafish gastrulation (52). Rab23 also has been found to interact with Pk and to control, albeit modestly, the cortical localization of PCP proteins (38). We hypothesized that endocytic trafficking was important for the accumulation of Pk within plasma membrane puncta, and that MINK1 could regulate that process.…”

Rabs on the fly: Functions of Rab GTPases during development

“…Second, large amounts of inactive cytosolic transgenic protein can mask the localization of the limited pool of active Rab proteins. [11][12][13][14]67 Genomic rescue constructs 41 in mutant backgrounds or manipulation of endogenous rab loci by homologous recombination 14 are powerful approaches that allow targeting the introduced tag for controlled Rab RNA and/or protein knock-down experiments. 42,68 Rab protein depletion Mutagenesis, RNAi knock-down or nanobody approaches reduce the entire cellular Rab protein pool.…”

Disruption of Wnt Planar Cell Polarity Signaling by Aberrant Accumulation of the MetAP-2 Substrate Rab37

“…Given that Rab37 levels increase in the presence of TNP-470, it is intriguing that a number of Rab proteins or their effectors have been shown to regulate Wnt PCP signaling (Lee, et al, 2007; Mottola, et al, 2010; Pataki, et al, 2010; Purvanov, et al, 2010). Thus we hypothesized that aberrant accumulation of Rab37 following inhibition of MetAP-2 may act via a ‘gain-of-function’ mechanism to disrupt Wnt PCP signaling, and as a result, endothelial cell homeostasis.…”