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.
Highlights
The centrosome consists of a pair centrioles surrounded by the pericentriolar matrix (PCM)
MTs are nucleated by γ-tubulin ring complex (γ-TuRC) that is targeted to the microtubule-organizing center (MTOC) [2]
Drosophila melanogaster centrosomin (CNN) is required for centrosomal maturation and recruitment of γ-TuRC onto centrosomes through its amino-terminal CNN Motif 1 (CM1) in CNN [3], which is highly conserved in mammalian CDK5RAP2, S. pombe Mto1p and Pcp1p [4, 5]
Summary
The centrosome consists of a pair centrioles surrounded by the pericentriolar matrix (PCM). Microtubules (MTs) are organized from the centrosome/microtubule-organizing center (MTOC) [1]. MTs are nucleated by γ-tubulin ring complex (γ-TuRC) that is targeted to the MTOC [2]. Drosophila melanogaster centrosomin (CNN) is required for centrosomal maturation and recruitment of γ-TuRC onto centrosomes through its amino-terminal CNN Motif 1 (CM1) in CNN [3], which is highly conserved in mammalian CDK5RAP2 ( known as Cep215), S. pombe Mto1p and Pcp1p [4, 5]. CDK5RAP2 is a functional human homolog of CNN required for a centrosomal maturation and planer spindle orientation in neuroblast, and PLOS ONE | DOI:10.1371/journal.pone.0140968. CDK5RAP2 is a functional human homolog of CNN required for a centrosomal maturation and planer spindle orientation in neuroblast, and PLOS ONE | DOI:10.1371/journal.pone.0140968 October 20, 2015
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
