Primary ciliogenesis requires the distal appendage component Cep123

Abstract

SummaryPrimary cilium formation is initiated at the distal end of the mother centriole in a highly co-ordinated manner. This requires the capping of the distal end of the mother centriole with a ciliary vesicle and the anchoring of the basal body (mother centriole) to the cell cortex, both of which are mediated by the distal appendages. Here, we show that the distal appendage protein Cep123 (Cep89/CCDC123) is required for the assembly, but not the maintenance, of a primary cilium. In the absence of Cep123 ciliary vesicle formation fails, suggesting that it functions in the early stages of primary ciliogenesis. Consistent with such a role, Cep123 interacts with the centriolar satellite proteins PCM-1, Cep290 and OFD1, all of which play a role in primary ciliogenesis. These interactions are mediated by a domain in the C-terminus of Cep123 (400–783) that overlaps the distal appendage-targeting domain (500–600). Together, the data implicate Cep123 as a new player in the primary ciliogenesis pathway and expand upon the role of the distal appendages in this process.

C2cd3 is critical for centriolar distal appendage assembly and ciliary vesicle docking in mammals

“…Multiple components of the centriolar distal appendages have been identified recently, including Ccdc41, Cep89, Sclt1, and Fbf1 (9,11,12,14). To study whether C2cd3 regulates the recruitment of additional distal appendage components, we transiently expressed GFP-tagged Ccdc41, Sclt1, Cep89, and Fbf1 in wild-type and C2cd3 GT mutant cells.…”

“…jax.org/marker/MGI:2141942), an inhibitor of ciliogenesis, from the distal end of the mother centriole (10). Recent studies have also suggested that components of the distal appendages are essential for docking ciliary vesicles to the mother centriole (9,(11)(12)(13)(14).…”

WDR8 is a centriolar satellite and centriole-associated protein that promotes ciliary vesicle docking during ciliogenesis

“…Vesicle docking at the mother centriole requires the presence of distal appendage components, including the proteins Cep164 and Cep123 (Schmidt et al, 2012;Sillibourne et al, 2013;Tanos et al, 2013). As assessed by TEM, distal appendages were present in WDR8-depleted cells (Fig.…”

“…Distal appendage proteins, including Cep164 and Cep123 (also known as Cep89), have been reported to be indispensable for this initial step of ciliary membrane biogenesis (Schmidt et al, 2012;Tanos et al, 2013;Joo et al, 2013;Sillibourne et al, 2013;Burke et al, 2014;Ye et al, 2014). Moreover, a cascade of small GTPases regulates vesicle docking and fusion at the mother centriole.…”

La poche ciliaire : fruit des liaisons du centrosome avec le trafic vésiculaire

“…Ces fibres de transition et la zone de transition à la base de l'axonème forment une structure agissant comme un filtre moléculaire qui contrôle le passage des protéines vers ou en dehors du cil. La composition des appendices distaux vient d'être récemment déterminée [11] : les protéines qui les constituent (PAD) ( Figure 1B) sont requises pour la formation des cils primaires [11][12][13][14][15]. CEP83 (centrosomal protein of 83-kDa)/CCDC41 (coiled-coil domain containing 41) joue un rôle central car elle est requise pour l'ancrage de toutes les autres protéines des appendices distaux au centriole père [11].…”