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bioRxiv · 10.1101/575225

C3G (RapGEF1) localizes to the mother centriole and regulates centriole division and primary cilia dynamics

Nayak, S. C.·Radha, V.
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Abstract

C3G (RapGEF1), a negative regulator of {beta}-catenin, plays a role in cell differentiation and is essential for early embryonic development in mice. In this study, we identify C3G as a centrosomal protein that regulates centriole division and primary cilia dynamics. C3G is present at the centrosome in interphase as well as mitotic cells, but is absent at the centrioles in differentiated myotubes. It interacts with, and co-localizes with cenexin in the mother centriole. Stable clone of cells depleted of C3G by CRISPR/Cas9 showed reduction in cenexin protein, and presence of supernumerary centrioles. Over-expression of C3G resulted in inhibition of centrosome division in normal and hydroxyurea treated cells. Proportion of ciliated cells is higher, and cilia length longer in C3G knockout cells. C3G inhibits cilia formation and length dependent on its catalytic activity. Unlike wild type cells, C3G depleted cells inefficiently retracted their cilia upon stimulation to reenter the cell cycle, and proliferated slowly, arresting in G1. We conclude that C3G inhibits centriole division and maintains ciliary homeostasis, properties that may be important for its role in embryonic development.\n\nSummary statementWe identify C3G as a centrosomal protein and regulator of centriole number, primary cilia length and resorption. These properties are important for its role in embryogenesis, and suggest that mutations in C3G could cause ciliopathies.

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Nayak, S. C., Radha, V.. 2019-03-12. C3G (RapGEF1) localizes to the mother centriole and regulates centriole division and primary cilia dynamics. https://doi.org/10.1101/575225

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