puc-header

CCDC57 Cooperates with Microtubules and Microcephaly Protein Cep63 and Regulates Centriole Duplication and Mitotic Progression

58 Pages Posted: 2 Oct 2019 Sneak Peek Status: Review Complete

See all articles by Kubra H. Zirhlioglu

Kubra H. Zirhlioglu

Koc University - Department of Molecular Biology and Genetics

Efraim Culfa

Koc University - Department of Molecular Biology and Genetics

Melis D. Arslanhan

Koc University - Department of Molecular Biology and Genetics

Elif Nur Firat-Karalar

Koc University - Department of Molecular Biology and Genetics

More...

Abstract

Centrosomes play critical roles in diverse cellular processes ranging from cell division to cellular signaling. At the core of the centrosomes are two centrioles, which duplicate only once per cell cycle and this duplication cycle is tightly regulated. Accordingly, their deregulation causes diseases such as cancer and developmental disorders like primary microcephaly. Complete understanding of the mechanisms that regulate centrosome biogenesis and function is required to elucidate the disease mechanisms. In this study, we identified a new centrosome protein CCDC57, which also localizes and binds to centriolar satellites and microtubules. Proximity-labeling and interaction studies showed that CCDC57 forms a complex with Cep63, centriolar satellites and microtubules. Importantly,characterization of CCDC57 deletion mutants revealed that its N-terminal 1-502 amino acid region mediated its centrosomal localization and interactions, whereas the C-terminal 606-916 amino acid region mediated its localization and binding to microtubules. Loss of CCDC57 causes defects in canonical centriole duplication and centriole amplification, and results in a failure to localize microcephaly-associated proteins Cep63 and Cep152 to the centriole during initiation of centriole duplication. Additionally, CCDC57 depletion resulted in prolonged mitosis, increased apoptosis and a higher ratio of mitotic defects such as misaligned chromosomes and multipolar spindles. Together, our results identify CCDC57 as dual regulator of the Cep63 centriole duplication module and microtubule-mediated mitotic processes and provide new mechanistic insight into defects underlying cancer and primary microcephaly.

Keywords: centriole duplication, Cep63, primary cilium, centriolar satellites, microcephaly, mitotic progression, microtubules

Suggested Citation

Zirhlioglu, Kubra H. and Culfa, Efraim and Arslanhan, Melis D. and Firat-Karalar, Elif Nur, CCDC57 Cooperates with Microtubules and Microcephaly Protein Cep63 and Regulates Centriole Duplication and Mitotic Progression (September 30, 2019). Available at SSRN: https://ssrn.com/abstract=3461784 or http://dx.doi.org/10.2139/ssrn.3461784
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Kubra H. Zirhlioglu

Koc University - Department of Molecular Biology and Genetics

Turkey

Efraim Culfa

Koc University - Department of Molecular Biology and Genetics

Turkey

Melis D. Arslanhan

Koc University - Department of Molecular Biology and Genetics

Turkey

Elif Nur Firat-Karalar (Contact Author)

Koc University - Department of Molecular Biology and Genetics

Turkey

Click here to go to Cell.com

Paper statistics

Abstract Views
441
Downloads
9