Role of DZIP1-CBY-FAM92 transition zone complex in the basal body to membrane attachment and ciliary budding.

Cilia play important signaling or motile functions in various organisms. In Human, cilia dysfunctions are responsible for a wide range of diseases, called ciliopathies. Cilia assembly is a tightly controlled process, which starts with the conversion of the centriole into a basal body, leading to the formation of the ciliary bud that protrudes inside a ciliary vesicle and/or ultimately at the cell surface. Ciliary bud formation is associated with the assembly of the transition zone (TZ), a complex architecture of proteins of the ciliary base which plays critical functions in gating proteins in and out of the ciliary compartment. Many proteins are involved in the assembly of the TZ, which shows structural and functional variations in different cell types or organisms. In this review, we discuss how a particular complex, composed of members of the DZIP1, CBY and FAM92 families of proteins, is required for the initial stages of cilia assembly leading to ciliary bud formation and how their functional hierarchy contributes to TZ assembly. Moreover, we summarize how evidences in Drosophila reveal functional differences of the DZIP1-CBY-FAM92 complex in the different ciliated tissues of this organism. Whereas it is essential for proper TZ assembly in the two types of ciliated tissues, it is involved in stable anchoring of basal bodies to the plasma membrane in male germ cells. Overall, the DZIP1-CBY-FAM92 complex reveals a molecular assembly pathway required for the initial stages of ciliary bud formation and that is conserved from Drosophila to Human.

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

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.

salto/CG13164 is required for sperm head morphogenesis in Drosophila.

Producing mature spermatozoa is essential for sexual reproduction in metazoans. Spermiogenesis involves dramatic cell morphological changes going from sperm tail elongation and nuclear reshaping to cell membrane remodeling during sperm individualization and release. The sperm manchette plays a critical scaffolding function during nuclear remodeling by linking the nuclear lamina to the cytoskeleton. Here, we describe the role of an uncharacterized protein in Drosophila, salto/CG13164, involved in nuclear shaping and spermatid individualization. Salto has dynamic localization during spermatid differentiation, being progressively relocated from the sperm-nuclear dense body, which is equivalent to the mammalian sperm manchette, to the centriolar adjunct and acrosomal cap during spermiogenesis. salto-null male flies are sterile and exhibit complete spermatid individualization defects. salto-deficient spermatids show coiled spermatid nuclei at late maturation stages and stalled individualization complexes. Our work sheds light on a novel component involved in cytoskeleton-based cell-morphological changes during spermiogenesis.

Transition zone assembly and its contribution to axoneme formation in Drosophila male germ cells.

The ciliary transition zone (TZ) is a complex structure found at the cilia base. Defects in TZ assembly are associated with human ciliopathies. In most eukaryotes, three protein complexes (CEP290, NPHP, and MKS) cooperate to build the TZ. We show that in Drosophila melanogaster, mild TZ defects are observed in the absence of MKS components. In contrast, Cby and Azi1 cooperate to build the TZ by acting upstream of Cep290 and MKS components. Without Cby and Azi1, centrioles fail to form the TZ, precluding sensory cilia assembly, and no ciliary membrane cap associated with sperm ciliogenesis is made. This ciliary cap is critical to recruit the tubulin-depolymerizing kinesin Klp59D, required for regulation of axonemal growth. Our results show that Drosophila TZ assembly in sensory neurons and male germ cells involves cooperative actions of Cby and Dila. They further reveal that temporal control of membrane cap assembly by TZ components and microtubule elongation by kinesin-13 is required for axoneme formation in male germ cells.