The central scaffold protein CEP350 coordinates centriole length, stability, and maturation

Abstract

The centriole is the microtubule-based backbone that ensures integrity, function, and cell cycle–dependent duplication of centrosomes. Mostly unclear mechanisms control structural integrity of centrioles. Here, we show that the centrosome protein CEP350 functions as scaffold that coordinates distal-end properties of centrioles such as length, stability, and formation of distal and subdistal appendages. CEP350 fulfills these diverse functions by ensuring centriolar localization of WDR90, recruiting the proteins CEP78 and OFD1 to the distal end of centrioles and promoting the assembly of subdistal appendages that have a role in removing the daughter-specific protein Centrobin. The CEP350–FOP complex in association with CEP78 or OFD1 controls centriole microtubule length. Centrobin safeguards centriole distal end stability, especially in the compromised CEP350−/− cells, while the CEP350–FOP–WDR90 axis secures centriole integrity. This study identifies CEP350 as a guardian of the distal-end region of centrioles without having an impact on the proximal PCM part.

A disease-associated PPP2R3C-MAP3K1 phospho-regulatory module controls centrosome function

“…PPP2R3C-GFP was also observed at the distal end of pro-centrioles, indicating that it is recruited soon after new centrioles form. Notably, this localization pattern precisely matches the pattern observed for FOP and is highly similar to the reported localization of CEP350, 54 supporting the predicted close functional relationship between these proteins (Fig. 1F-G).…”

“…In prior studies, FOP and CEP350 have been found to regulate ciliogenesis, microtubule nucleation, centriole length, and centriole stability. 52,54,59,60 Thus, FOP and CEP350 likely regulate diverse centrosomal functions through PPP2R3C as well as by PPP2R3C-independent mechanisms.…”

Predicting potential target genes in molecular biology experiments using machine learning and multifaceted data sources

“… 47 Furthermore, although the other three genes were not analyzed in the articles, the transcripts of RTTN , CEP350 , and CCDC77 are also localized to the centrosome and appear to be worth analyzing. 48 , 49 , 50 These results illustrate that our model can generate reasonable suggestions for the query genes even without any functional information.…”

The maintenance of centriole appendages and motile cilia basal body anchoring relies on TBCCD1

“…The results show that TBCCD1 was critical to maintain CEP170 at the SDA and the proximal ends of centrioles. Finally, we also studied the impact of TBCCD1 RNAi in the fluorescence intensity and localization of the centriolar protein CEP350, which is required for the stability and formation of DA and SDA (Karasu et al, 2022), as well as for MT anchoring (Yan et al, 2006). Our results showed that TBCCD1 depletion caused a 39% decrease in CEP350 levels at the centrosome (n=119 centrosomes).…”

“…However, its depletion causes the loss of CEP170 from the tip of SDA, accompanied by the decrease of centriolar levels of Centriolin/CEP110 and Ninein (Figure 5). Similarly to TBCCD1, the CEP350 protein, a member of the TBCCD1 proximity interaction network (Figure 9), is required for DA and SDA assembly without being a component of those structures (Karasu et al, 2022). CEP350, which localizes between the FOP protein and the centriole's wall, is a key protein for regulating the length, stability, and assembly of the distal region of the centriole (Karasu et al, 2022).…”