Drosophila sensory cilia lacking MKS proteins exhibit striking defects in development but only subtle defects in adults

Abstract

Cilia are conserved organelles that have important motility, sensory and signalling roles. The transition zone (TZ) at the base of the cilium is crucial for cilia function, and defects in several TZ proteins are associated with human congenital ciliopathies such as nephronophthisis (NPHP) and Meckel–Gruber syndrome (MKS). In several species, MKS and NPHP proteins form separate complexes that cooperate with Cep290 to assemble the TZ, but flies seem to lack core components of the NPHP module. We show that MKS proteins in flies are spatially separated from Cep290 at the TZ, and that flies mutant for individual MKS genes fail to recruit other MKS proteins to the TZ, whereas Cep290 seems to be recruited normally. Although there are abnormalities in microtubule and membrane organisation in developing MKS mutant cilia, these defects are less apparent in adults, where sensory cilia and sperm flagella seem to function quite normally. Thus, localising MKS proteins to the cilium or flagellum is not essential for viability or fertility in flies.

Phosphatidylinositol 4,5-bisphosphate regulates cilium transition zone maturation in Drosophila melanogaster

“…Consistent with this result, the ultrastructure of BBs in β 2 t-SigD is normal, and localization of the centriolar marker GFP-PACT (Basto et al, 2006) is similar in control and β 2 t-SigD cells (Wei et al, 2008). In contrast, the TZ proteins Chibby (Cby) (Enjolras et al, 2012) and Mks1 (Vieillard et al, 2016;Pratt et al, 2016) exhibited hyperelongation in β 2 t-SigD cells (Fig. 1E), indicating that this phenotype is not unique to Cep290.…”

“…Similar to β 2 t-SigD, Drosophila dila; cby and cby mutants display hyperelongated TZs (Enjolras et al, 2012;Vieillard et al, 2016). In contrast, mks1 mutants have shorter TZs (Pratt et al, 2016). Because both Cby and Mks1 are hyperelongated in β 2 t-SigD cells, PIP 2 regulates TZ length independently of an effect on Cby or Mks1 recruitment.…”

“…(A) onr mutants do not display hyperelongated acetylated tubulin (Ac-tub) at the cilium (arrowheads). Acetylated tubulin marks the axoneme, which colocalizes with the TZ in spermatocytes (Pratt et al, 2016). Boxplots show length quantifications (bottom).…”

Centrioles and Ciliary Structures during Male Gametogenesis in Hexapoda: Discovery of New Models

“…It has been observed that in Drosophila the ciliary projections of neurons of type I elongate through a mechanism mediated by an intraflagellar transport (IFT) mechanism [140,141], namely the compartmentalized pathway of assembly [142]. The base of the sensory cilia in Drosophila displays Y-links [68,90] and contains some conserved transition zone (TZ) module proteins [89][90][91]143]. This suggests that this region can be regarded as a typical TZ, a specialized domain found at the boundary between the basal body and the axoneme in primary cilia and directly involved in their assembly and maintenance.…”

“…An additional question is the elongation mechanism of the CLRs. Although the CLRs of Drosophila spermatocytes diverge from the conventional primary cilia, they share with vertebrate cilia some conserved TZ module proteins [87][88][89]143,154]. The CLRs are assembled in Drosophila by IFT-independent mechanisms [155] and it has been proposed that their grow requires components directly recruited from the cytoplasm, namely the cytosolic pathway of assembly [142].…”