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Axonal/Dendritic Growth and Circuit Formation

開催日 2014/9/13
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

ERK2-Mediated Phosphorylation of Par3 Regulates Neuronal Polarization

  • P3-064
  • 船橋 靖広 / Yasuhiro Funahashi:1 難波 隆志 / Takashi Namba:1 藤末 慎 / Shin Fujisue:1 伊藤 教道 / Norimichi Ito:1 中牟田 信一 / Shinichi Nakamuta:1 加藤 勝洋 / Katsuhiro Kato:1 島田 明子 / Akiko Shimada:1 Xu Chundi / Chundi Xu:1 Shan Wei / Wei Shan:1 西岡 朋生 / Tomoki Nishioka:1 貝淵 弘三 / Kozo Kaibuchi:1 
  • 1:名古屋大学 / Dept. of Cell Pharmacology, Grad. Sch. of Med., Nagoya Univ. 

Axon formation is one of the most important events in neuronal polarization and is regulated by signaling molecules involved in cytoskeletal rearrangement and protein transport. We previously found that Partition-defective 3 (Par3) is associated with KIF3A (kinesin-2) and is trans- ported into the nascent axon in a KIF3A-dependent fashion. Par3 interacts with the Rac-specific guanine nucleotide-exchange factors (GEFs) Tiam1/2, which activate Rac1, and participates in axon formation in cultured hippocampal neurons. However, the regulatory mechanism of the Par3-KIF3A interaction is poorly understood, and the role of Par3 in neuronal polarization in vivo remains elusive. Here, we found that extra- cellular signal-regulated kinase 2 (ERK2) directly interacts with Par3, that ERK2 phosphorylates Par3 at Ser-1116, and that the phosphorylated Par3 accumulates at the axonal tips in a manner dependent upon ERK2 activity. The phosphorylation of Par3 by ERK2 inhibited the interaction of Par3 with KIF3A but not with the other Par3 partners, including Par6 and aPKC. The phosphomimic mutant of Par3 (Par3-S1116D) showed less binding activity with the KIF3s and slower transport in the axons. The knockdown of Par3 by RNA interference impaired neuronal polar- ization, which was rescued with RNAi-resistant Par3, but not with the phosphomimic Par3 mutant, in cultured rat hippocampal neurons and mouse cortical projection neurons in vivo. These results suggest that ERK2 phosphorylates Par3 and inhibits its binding with KIF3A, thereby controlling Par3 transport and neuronal polarity.

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