| The centrosome is a collection of proteins scaffolded upon microtubule based structures called centrioles. Centrosomes play critical roles as the primary microtubule organizing centers in interphase and mitotic cells, and template the formation of cilia and flagella. A mitotic cell contains two centrosomes, each with two centrioles, and following mitosis daughter cells inherit one centrosome. Before the next mitotic division, centrioles are duplicated in a process where one procentriole forms adjacent to each existing centriole. Mutations in proteins required for centriole duplication and/or centrosome function cause developmental defects such as primordial dwarfism, microcephaly and ciliopathies. Additionally many tumor cells contain excess centrosomes, and extra centrosomes are a driver of cancer progression. Thus, the correct number and function of centrosomes is critical for human health, and understanding the proteins involved in centriole assembly will offer insights into important diseases. Here, I describe the functions of CEP120 and SPICE1 as proteins required for centriole assembly. I show that CEP120 and SPICE1 cooperate with CPAP in the assembly of centrioles. Within the centriole duplication pathway, CEP120 and SPICE1 are dependent upon the presence of SASS6, STIL, CPAP and CEP135, and are in turn required for CEP135, CP110, CEP97 and Centrin recruitment. Further, CEP120 interacts with CPAP, and they cooperate with SPICE1 in centriole microtubule assembly and elongation. Following up on this work, I identify a group of proteins with previously undescribed roles in centriole duplication, including the human nucleosome assembly protein NAP1L1. These proteins were identified by screening for proteins in the proximity of CEP120 and SPICE1, and several of them are important for centriole elongation, suggesting a functional link to CEP120 and SPICE1 in centriole assembly. The results herein represent important advances in our understanding of how CEP120 and SPICE1 function, and in our understanding of centriole assembly and elongation.. |
