An essential role of the aPKC-Aurora A-NDEL1 pathway in neurite elongation by modulation of microtubule dynamics.
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.
Mori
Daisuke
D
Department of Genetic Disease Research, Osaka City University, Japan.
Yamada
Masami
M
Mimori-Kiyosue
Yuko
Y
Shirai
Yasuhito
Y
Suzuki
Atsushi
A
Ohno
Shigeo
S
Saya
Hideaki
H
Wynshaw-Boris
Anthony
A
Hirotsune
Shinji
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D064096:Aurora Kinase A; D064127:Aurora Kinases; D002352:Carrier Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D005727:Ganglia, Spinal / Q000201:enzymology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D022101:Microtubule-Organizing Center / Q000201:enzymology; D008870:Microtubules / Q000201:enzymology*; D008938:Mitosis; D018716:Molecular Mimicry; D009154:Mutation / Q000235:genetics; D016501:Neurites / Q000201:enzymology*; D010766:Phosphorylation; D010769:Phosphothreonine / Q000378:metabolism; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D008869:Microtubule-Associated Proteins; C486015:Ndel1 protein, mouse; D010769:Phosphothreonine; C576918:Aurka protein, mouse; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; C115015:PKC-3 protein; D011493:Protein Kinase C