Regulation of Centriole Length by the Distal Tip Complex

Abstract

The centrosome is a tiny organelle that builds and coordinates complex microtubule machines in cells. Centrioles, the core components of each centrosome, are barrel-shaped structures with intricate architecture. Establishing and maintaining proper centriole structure is critical for proper centrosome function; however, deciphering mechanisms underlying centriole assembly remains a major hurdle in the field of centrosome biology. To address this gap, I sought to elucidate mechanisms by which the centriole grows. Herein, I focus on a key question in the field: How do the proteins that reside at the distal tip of the centriole coordinate processive growth during specific stages of centriole biogenesis? First, I identify a novel component of the conserved distal tip complex, Cep104, that promotes centriole growth. Second, I decipher a mechanism regulating activity of the key centriolar kinase Polo-like Kinase 4 and provide a potential role for the kinase in regulating the distal tip complex. By combining these findings with a detailed distal tip interactome, I develop a hypothetical model of centriole assembly integrating our genetic understanding of centriole growth with my novel molecular mechanisms.