CEP120 and SPICE1 Cooperate with CPAP in Centriole Elongation

Abstract

Centrosomes organize microtubule (MT) arrays and are comprised of centrioles surrounded by ordered pericentriolar proteins. Centrioles are barrel-shaped structures composed of MTs, and as basal bodies they template the formation of cilia/flagella. Defects in centriole assembly can lead to ciliopathies and genome instability. The assembly of procentrioles requires a set of conserved proteins. It is initiated at the G1-to-S transition by PLK4 and CEP152, which help recruit SASS6 and STIL to the vicinity of the mother centriole to organize the cartwheel. Subsequently, CPAP promotes centriolar MT assembly and elongation in G2. While centriole integrity is maintained by CEP135 and POC1 through MT stabilization, centriole elongation requires POC5 and is restricted by CP110 and CEP97. How strict control of centriole length is achieved remains unclear. Here, we show that CEP120 and SPICE1 are required to localize CEP135 (but not SASS6, STIL, or CPAP) to procentrioles. CEP120 associates with SPICE1 and CPAP, and depletion of any of these proteins results in short procentrioles. Furthermore, CEP120 or CPAP overexpression results in excessive centriole elongation, a process dependent on CEP120, SPICE1, and CPAP. Our findings identify a shared function for these proteins in centriole length control.

Centrobin-mediated Regulation of the Centrosomal Protein 4.1-associated Protein (CPAP) Level Limits Centriole Length during Elongation Stage

“…Although several centriolar proteins such as STIL, SAS-6, CEP120, SPICE1, and CEP135 can interact with CPAP and positively regulate the centriole duplication and elongation process (30,32,45,46), this is the first study that uncovers the mechanism by which CPAP levels are regulated in the cell to restrict the centriole length. Earlier we showed that centrobin binds to CPAP directly, and this interaction is essential for maintaining CPAP levels on centrioles (48).…”

“…Interestingly, the elongation phase of centriole duplication, which determines centriole length, is completed by the time cells reach mitosis (44). Although CEP120 and SPICE1 are known to promote centriole elongation and interact with CPAP (45,46), they act downstream of CPAP in the centriole duplication process. Therefore, identifying the upstream targets and underlying signals that govern cellular CPAP levels will shed light on how the centriole length is restricted.…”

Quantitative analysis of human centrosome architecture by targeted proteomics and fluorescence imaging

“…The protein CPAP gets recruited to promote the assembly of microtubules onto the cartwheel (Tang et al , 2011a; Cottee et al , 2013; Sharma et al , 2016), and this step is likely assisted by Cep135 (the human homolog of Chlamydomonas Bld10) (Hirono, 2014). CPAP also cooperates with additional proteins, including CP110, in determining the length of nascent centrioles (Kohlmaier et al , 2009; Schmidt et al , 2009; Tang et al , 2009; Comartin et al , 2013; Lin et al , 2013; Sharma et al , 2016). Finally, centriole maturation is completed by the acquisition of subdistal and distal appendages (Paintrand et al , 1992; Tateishi et al , 2013).…”

The Centrosome and Its Duplication Cycle

“…Some of the components identified as essential for centriole assembly also contribute to centriolar microtubule elongation. Sas-4/ CPAP, for example, promotes the polymerization of centriolar microtubules in cooperation with CEP120, which localizes preferentially to the daughter centriole Comartin et al 2013;Lin et al 2013b). Overexpression of either CPAP or CEP120 results in excessively long centrioles and their depletion abolishes this phenotype (Comartin et al 2013;Lin et al 2013b).…”

“…Sas-4/ CPAP, for example, promotes the polymerization of centriolar microtubules in cooperation with CEP120, which localizes preferentially to the daughter centriole Comartin et al 2013;Lin et al 2013b). Overexpression of either CPAP or CEP120 results in excessively long centrioles and their depletion abolishes this phenotype (Comartin et al 2013;Lin et al 2013b). CEP120 also interacts with SPICE1 that is required for centriole duplication, spindle formation, and chromosome congression (Archinti et al 2010).…”