NDEL1 phosphorylation by Aurora-A kinase is essential for centrosomal maturation, separation, and TACC3 recruitment.
NDEL1 is a binding partner of LIS1 that participates in the regulation of cytoplasmic dynein function and microtubule organization during mitotic cell division and neuronal migration. NDEL1 preferentially localizes to the centrosome and is a likely target for cell cycle-activated kinases, including CDK1. In particular, NDEL1 phosphorylation by CDK1 facilitates katanin p60 recruitment to the centrosome and triggers microtubule remodeling. Here, we show that Aurora-A phosphorylates NDEL1 at Ser251 at the beginning of mitotic entry. Interestingly, NDEL1 phosphorylated by Aurora-A was rapidly downregulated thereafter by ubiquitination-mediated protein degradation. In addition, NDEL1 is required for centrosome targeting of TACC3 through the interaction with TACC3. The expression of Aurora-A phosphorylation-mimetic mutants of NDEL1 efficiently rescued the defects of centrosomal maturation and separation which are characteristic of Aurora-A-depleted cells. Our findings suggest that Aurora-A-mediated phosphorylation of NDEL1 is essential for centrosomal separation and centrosomal maturation and for mitotic entry.
Mori
Daisuke
D
Osaka City University Graduate School of Medicine, Genetic Disease Research, Asahi-machi 1-4-3 Abeno, Osaka 545-8586, Japan.
Yano
Yoshihisa
Y
Toyo-oka
Kazuhito
K
Yoshida
Noriyuki
N
Yamada
Masami
M
Muramatsu
Masami
M
Zhang
Dongwei
D
Saya
Hideyuki
H
Toyoshima
Yoko Y
YY
Kinoshita
Kazuhisa
K
Wynshaw-Boris
Anthony
A
Hirotsune
Shinji
S
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D064096:Aurora Kinase A; D064127:Aurora Kinases; D002352:Carrier Proteins / Q000378:metabolism* / Q000502:physiology*; D002465:Cell Movement; D018385:Centrosome / Q000378:metabolism*; D005326:Fetal Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D000074201:Katanin; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism
D002352:Carrier Proteins; D005326:Fetal Proteins; D008869:Microtubule-Associated Proteins; C421108:NDEL1 protein, human; C486015:Ndel1 protein, mouse; C120551:TACC3 protein, human; C418485:TACC3 protein, mouse; D025801:Ubiquitin; C576918:Aurka protein, mouse; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D000251:Adenosine Triphosphatases; D000074201:Katanin