CEP295, also known as Ana1 in Drosophila, is an essential protein for centrosome and centriole maintenance. Centrosomes and centrioles are microtubule-organizing centers (MTOC) with diverse functions. CEP295 is involved in pathways related to centriole elongation, centriole-to-centrosome conversion, and maintaining centrosome structural integrity [1,2,3,6]. Its proper function is crucial for normal cell division, cilia formation, and overall cellular development, and genetic models are valuable for studying its functions.

Depletion of CEP295 in cell lines and patient-derived fibroblasts leads to a decrease in centriole and centrosome numbers, triggering p53-dependent G1 cell cycle arrest [4]. It is required for building the distal half centrioles and post-translational modification of centriolar microtubules; without it, the recruitments of POC5 and POC1B to the distal half centrioles are inhibited, resulting in shorter centrioles [2]. In the absence of PPP1R35, nascent centrioles cannot recruit CEP295, and they become disintegrated after mitosis [5]. Also, CEP295 is necessary for the conversion of daughter centrioles into functional mother centrioles, acting upstream of the conserved pathway for centriole formation [3].

In conclusion, CEP295 is vital for centriole and centrosome-related biological functions such as centriole elongation, conversion, and maintenance of structural integrity. Model-based research, especially loss-of-function experiments, has revealed its significance. Bi-allelic variants in CEP295 cause Seckel-like syndrome in humans, characterized by primary microcephaly, developmental delay, intellectual disability, short stature, and craniofacial and digital abnormalities [4].

References:

1. Pimenta-Marques, Ana, Perestrelo, Tania, Reis-Rodrigues, Patricia, Lince-Faria, Mariana, Bettencourt-Dias, Mónica. 2024. Ana1/CEP295 is an essential player in the centrosome maintenance program regulated by Polo kinase and the PCM. In EMBO reports, 25, 102-127. doi:10.1038/s44319-023-00020-6. https://pubmed.ncbi.nlm.nih.gov/38200359/

2. Chang, Ching-Wen, Hsu, Wen-Bin, Tsai, Jhih-Jie, Tang, Chieh-Ju C, Tang, Tang K. 2016. CEP295 interacts with microtubules and is required for centriole elongation. In Journal of cell science, 129, 2501-13. doi:10.1242/jcs.186338. https://pubmed.ncbi.nlm.nih.gov/27185865/

3. Tsuchiya, Yuki, Yoshiba, Satoko, Gupta, Akshari, Watanabe, Koki, Kitagawa, Daiju. 2016. Cep295 is a conserved scaffold protein required for generation of a bona fide mother centriole. In Nature communications, 7, 12567. doi:10.1038/ncomms12567. https://pubmed.ncbi.nlm.nih.gov/27562453/

4. Li, Niu, Xu, Yufei, Chen, Hongzhu, Machol, Keren, Wang, Jian. 2023. Bi-allelic variants in CEP295 cause Seckel-like syndrome presenting with primary microcephaly, developmental delay, intellectual disability, short stature, craniofacial and digital abnormalities. In EBioMedicine, 99, 104940. doi:10.1016/j.ebiom.2023.104940. https://pubmed.ncbi.nlm.nih.gov/38154379/

5. Fong, Chii Shyang, Ozaki, Kanako, Tsou, Meng-Fu Bryan. 2018. PPP1R35 ensures centriole homeostasis by promoting centriole-to-centrosome conversion. In Molecular biology of the cell, 29, 2801-2808. doi:10.1091/mbc.E18-08-0525. https://pubmed.ncbi.nlm.nih.gov/30230954/

6. Izquierdo, Denisse, Wang, Won-Jing, Uryu, Kunihiro, Tsou, Meng-Fu Bryan. 2014. Stabilization of cartwheel-less centrioles for duplication requires CEP295-mediated centriole-to-centrosome conversion. In Cell reports, 8, 957-65. doi:10.1016/j.celrep.2014.07.022. https://pubmed.ncbi.nlm.nih.gov/25131205/