TY - JOUR
T1 - An essential role of the aPKC-Aurora A-NDEL1 pathway in neurite elongation by modulation of microtubule dynamics
AU - Mori, Daisuke
AU - Yamada, Masami
AU - Mimori-Kiyosue, Yuko
AU - Shirai, Yasuhito
AU - Suzuki, Atsushi
AU - Ohno, Shigeo
AU - Saya, Hideaki
AU - Wynshaw-Boris, Anthony
AU - Hirotsune, Shinji
PY - 2009
Y1 - 2009
N2 - Orchestrated remodelling of the cytoskeketon is prominent during neurite extension. In contrast with the extensive characterization of actin filament regulation, little is known about the dynamics of microtubules during neurite extension. Here we identify an atypical protein kinase C (aPKC)-Aurora A-NDEL1 pathway that is crucial for the regulation of microtubule organization during neurite extension. aPKC phosphorylates Aurora A at Thr 287 (T287), which augments interaction with TPX2 and facilitates activation of Aurora A at the neurite hillock, followed by phosphorylation of NDEL1 at S251 and recruitment. Suppression of aPKC, Aurora A or TPX2, or disruption of Ndel1, results in severe impairment of neurite extension. Analysis of microtubule dynamics with a microtubule plus-end marker revealed that suppression of the aPKC-Aurora A-NDEL1 pathway resulted in a significant decrease in the frequency of microtubule emanation from the microtubule organizing centre (MTOC), suggesting that Aurora A acts downstream of aPKC. These findings demonstrate a surprising role of aPKC-Aurora A-NDEL1 pathway in microtubule remodelling during neurite extension.
AB - Orchestrated remodelling of the cytoskeketon is prominent during neurite extension. In contrast with the extensive characterization of actin filament regulation, little is known about the dynamics of microtubules during neurite extension. Here we identify an atypical protein kinase C (aPKC)-Aurora A-NDEL1 pathway that is crucial for the regulation of microtubule organization during neurite extension. aPKC phosphorylates Aurora A at Thr 287 (T287), which augments interaction with TPX2 and facilitates activation of Aurora A at the neurite hillock, followed by phosphorylation of NDEL1 at S251 and recruitment. Suppression of aPKC, Aurora A or TPX2, or disruption of Ndel1, results in severe impairment of neurite extension. Analysis of microtubule dynamics with a microtubule plus-end marker revealed that suppression of the aPKC-Aurora A-NDEL1 pathway resulted in a significant decrease in the frequency of microtubule emanation from the microtubule organizing centre (MTOC), suggesting that Aurora A acts downstream of aPKC. These findings demonstrate a surprising role of aPKC-Aurora A-NDEL1 pathway in microtubule remodelling during neurite extension.
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U2 - 10.1038/ncb1919
DO - 10.1038/ncb1919
M3 - Article
C2 - 19668197
AN - SCOPUS:69949167012
SN - 1465-7392
VL - 11
SP - 1057
EP - 1068
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 9
ER -