Faculty Opinions recommendation of CEP120 interacts with C2CD3 and Talpid3 and is required for centriole appendage assembly and ciliogenesis.

Centrosomal protein 120 (CEP120) was originally identified as a daughter centriole-enriched protein that participates in centriole elongation.Recent studies showed that CEP120 gene mutations cause complex ciliopathy phenotypes in humans, including Joubert syndrome and Jeune asphyxiating thoracic dystrophy, suggesting that CEP120 plays an additional role in ciliogenesis.To investigate the potential roles of CEP120 in centriole elongation and cilia formation, we knocked out the CEP120 gene in p53-deficient RPE1 cells using the CRISPR/Cas9 editing system, and performed various analyses.We herein report that loss of CEP120 produces short centrioles with no apparent distal and subdistal appendages.CEP120 knockout was also associated with defective centriole elongation, impaired recruitment of C2CD3 and Talpid3 to the distal ends of centrioles, and consequent defects in centriole appendage assembly and cilia formation.Interestingly, wild-type CEP120 interacts with C2CD3 and Talpid3, whereas a disease-associated CEP120 mutant (I975S) has a low affinity for C2CD3 binding and perturbs cilia assembly.Together, our findings reveal a novel role of CEP120 in ciliogenesis by showing that it interacts with C2CD3 and Talpid3 to assemble centriole appendages and by illuminating the molecular mechanism through which the CEP120 (I975S) mutation causes complex ciliopathies.Centrioles are microtubule (MT)-based organelles that exist as part of the centrosome and are also essential for the formation of cell structures known as cilia and flagella.Centriole duplication starts at the G1-S transition of the cell cycle.A nascent centriole (daughter centriole) starts to grow from the proximal end of a pre-existing centriole (mother centriole) in G1 phase of cell cycle, elongates through the S and G2 phases, and reaches its full length at early mitosis.In this cell cycle, the daughter centriole has not yet acquired subdistal appendages (SDAs) and distal appendages (DAs), cannot be basal body for primary cilia, but can produce new daughter centriole near the proximal end 1-5 .After its second round of mitosis, this centriole becomes a fully mature mother centriole [1][2][3][4][5] .The primary cilium is a hair-like MT-based structure that protrudes from the cell surface and is responsible for sensing extracellular signals and regulating cell homeostasis and development.We previously showed that myosin-Va mediates the transportation of preciliary vesicles (PCVs) to the DA of a mother centriole as the earliest event that defines the onset of ciliogenesis 6 .These PCVs fuse with other incoming PCVs to form a large ciliary vesicle through the membrane shaping proteins EHD1 and EHD3 7 .This initial step that converts the mother centriole into a basal body, is followed by removal of the centriolar coiled coil protein 110 (CP110) that caps the distal end of the mother centriole, the assembly of ciliary transition zone, and the growth of axoneme microtubules during ciliogenesis 8 .A current model holds that centriole duplication occurs after activation of PLK4, followed by assembling a SAS-6-containing cartwheel at the proximal end of mother centriole 9-14 .CEP135 serves as a bridge molecule that connects SAS-6 and CPAP, linking the cartwheel to the centriolar MTs 15 .CPAP then acts together with CEP120 and SPICE to promote the assembly and elongation of centriolar MTs during S/G2 phase 16,17 .However, we do not yet fully understand the molecular basis through which a full-length centriole assembles its own SDAs and DAs to become a mature centriole and how a mature centriole is converted to a basal body to initiate ciliogenesis.C2CD3 and Talpid3 are evolutionarily conserved genes essential for vertebrate development and ciliogenesis [18][19][20][21][22] .Recent studies showed that C2CD3 is required for the recruitment of centriolar DA proteins 21 and loss of C2CD3 results institute of Biomedical Sciences, Academia Sinica, taipei, taiwan.

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