Dzip1 and Fam92 form a ciliary transition zone complex with cell type specific roles in Drosophila

Abstract

Cilia and flagella are conserved eukaryotic organelles essential for cellular signaling and motility. Cilia dysfunctions cause life-threatening ciliopathies, many of which are due to defects in the transition zone (TZ), a complex structure of the ciliary base. Therefore, understanding TZ assembly, which relies on ordered interactions of multiprotein modules, is of critical importance. Here, we show that Drosophila Dzip1 and Fam92 form a functional module which constrains the conserved core TZ protein, Cep290, to the ciliary base. We identify cell type specific roles of this functional module in two different tissues. While it is required for TZ assembly in all Drosophila ciliated cells, it also regulates basal-body growth and docking to the plasma membrane during spermatogenesis. We therefore demonstrate a novel regulatory role for Dzip1 and Fam92 in mediating membrane/basal-body interactions and show that these interactions exhibit cell type specific functions in basal-body maturation and TZ organization.

CEP290 is essential for the initiation of ciliary transition zone assembly

“…Additionally, deletion of DZIP1 resulted in the separation of the BBs and the plasma membrane in late spermatocytes ( Fig 4I ). All these observations are consistent with the recent report [ 29 ], indicating that like CEP290, DZIP1 is essential for TZ assembly initiation.…”

“…To investigate the functional relationship between CEP290 and DZIP1, we generated a deletion mutant of dzip1 ΔC (c.1069-1529Del), in which the C-terminus (aa 357-end) of DZIP1 is lost ( S5A–S5C Fig ). Consistent with the recent report [ 29 ], dzip1 mutant exhibited typical cilia mutant phenotypes. The flies were completely uncoordinated, unable even to stand, and were severely deficient in touch and hearing ( S5D Fig ).…”

“…Similar to previously reported alleles [ 24 , 29 ], both cep290 1 and cep290 ΔC were severely uncoordinated during walking and flying, and they had severe defects in both touch sensitivity and hearing sensation ( S1E Fig ), typical phenotypes of cilia deficiency mutants. Importantly, all these defects could be rescued by expression of UAS-cep290 under the pan-neural driver elav-GAL4 ( S1E Fig ).…”

“…While the role of Drosophila DZIP1 in ciliogenesis was unknown when we started this project, a recent study showed that DZIP1 was localized to the TZ and was required for ciliogenesis in Drosophila [ 29 ]. Consistent with this report, we observed that Drosophila DZIP1 localized to the basal body in all cilia examined ( S4A and S4B Fig ).…”

Rpgrip1l controls ciliary gating by ensuring the proper amount of Cep290 at the vertebrate transition zone

“…For this reason, the assembly and function of the TZ is a hot topic in biomedical research. A lot of proteins participate in TZ assembly and/or function as ciliary gatekeepers at the TZ [12- 14,16,17,19,23,24,27,29,30,33,34,37,41,69,70,[73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][89][90]. However, the relationships between these proteins and hence the mechanisms underlying ciliary gating at the TZ remain largely elusive.…”