Cep169, a Novel Microtubule Plus-End-Tracking Centrosomal Protein, Binds to CDK5RAP2 and Regulates Microtubule Stability

Abstract

The centrosomal protein, CDK5RAP2, is a microcephaly protein that regulates centrosomal maturation by recruitment of a γ-tubulin ring complex (γ-TuRC) onto centrosomes. In this report, we identified a novel human centrosomal protein, Cep169, as a binding partner of CDK5RAP2, a member of microtubule plus-end-tracking proteins (+TIPs). Cep169 interacts directly with CDK5RAP2 through CM1, an evolutionarily conserved domain, and colocalizes at the pericentriolar matrix (PCM) around centrioles with CDK5RAP2. In addition, Cep169 interacts with EB1 through SxIP-motif responsible for EB1 binding, and colocalizes with CDK5RAP2 at the microtubule plus-end. EB1-binding–deficient Cep169 abolishes EB1 interaction and microtubule plus-end attachment, indicating Cep169 as a novel member of +TIPs. We further show that ectopic expression of either Cep169 or CDK5RAP2 induces microtubule bundling and acetylation in U2OS cells, and depletion of Cep169 induces microtubule depolymerization in HeLa cells, although Cep169 is not required for assembly of γ-tubulin onto centrosome by CDK5RAP2. These results show that Cep169 targets microtubule tips and regulates stability of microtubules with CDK5RAP2.

Circular Trajectory Reconstruction Uncovers Cell‐Cycle Progression and Regulatory Dynamics from Single‐Cell Hi‐C Maps

“…[33] It overlaps with the anchor of a loop formed from MS to MS-G2 phase ( Figure 5A). [33] It overlaps with the anchor of a loop formed from MS to MS-G2 phase ( Figure 5A).…”

Effector gene expression underlying neuron subtype-specific traits in the Motor Ganglion of Ciona

“…Similarly, Nckap5 is an ortholog of the closely related human paralogs NCKAP5 and NCKAP5L. In mammals, NCKAP5L encodes Cep169, a centrosome-enriched protein that also stabilizes microtubules (Mori et al, 2015a(Mori et al, , 2015b. In our profiling, a single probeset detected enrichment of Saxo, but fragmented annotation of earlier versions of the C. robusta genome resulted in at least 5 independent probesets that we manually annotated as covering the updated Nckap5 gene model (KH.C9.229).…”

Polo-like kinase 4 maintains centriolar satellite integrity by phosphorylation of centrosomal protein 131 (CEP131)

“…Two centrosome proteins identified in our screen, CEP152 and PCM1, were previously identified as PLK4 substrates (Table 1), providing credence that this screening approach identified PLK4 substrates. From the remaining list, we selected the proteins known to be associated with centriole duplication: CEP131 (7,49), CEP215/ CDK5RAP2 (50), and CEP350 (51). None of these proteins have been previously identified as PLK4 substrates.…”