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.
| Original language | English |
|---|---|
| Article number | e0140968 |
| Journal | PLoS One |
| Volume | 10 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2015 Oct 20 |
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ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
Cep169, a novel microtubule plus-end-tracking centrosomal protein, binds to CDK5RAP2 and regulates microtubule stability. / Mori, Yusuke; Inoue, Yoko; Tanaka, Sayori; Doda, Satoka; Yamanaka, Shota; Fukuchi, Hiroki; Terada, Yasuhiko.
In: PLoS One, Vol. 10, No. 10, e0140968, 20.10.2015.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cep169, a novel microtubule plus-end-tracking centrosomal protein, binds to CDK5RAP2 and regulates microtubule stability
AU - Mori, Yusuke
AU - Inoue, Yoko
AU - Tanaka, Sayori
AU - Doda, Satoka
AU - Yamanaka, Shota
AU - Fukuchi, Hiroki
AU - Terada, Yasuhiko
PY - 2015/10/20
Y1 - 2015/10/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84946578773&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84946578773&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0140968
DO - 10.1371/journal.pone.0140968
M3 - Article
C2 - 26485573
AN - SCOPUS:84946578773
VL - 10
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 10
M1 - e0140968
ER -