Research Abstract



Doublecortin-like kinase enhances dendritic remodelling and negatively regulates synapse maturation

2013年2月5日 Nature Communications 4 : 1440 doi: 10.1038/ncomms2443


申 義庚1, 柏木 有太郎1, 栗生 俊彦2, 岩崎 広英1, 田中 輝幸3, 古泉 博之4, Joseph G. Gleeson4 & 岡部 繁男1

  1. 東京大学大学院 医学系研究科 神経細胞生物学分野
  2. 徳島文理大学 香川薬学部 神経科学研究所
  3. 東京大学大学院 医学系研究科 発達医科学分野
  4. カリフォルニア大学サンディエゴ校(米国)
Dendritic morphogenesis and formation of synapses at appropriate dendritic locations are essential for the establishment of proper neuronal connectivity. Recent imaging studies provide evidence for stabilization of dynamic distal branches of dendrites by the addition of new synapses. However, molecules involved in both dendritic growth and suppression of synapse maturation remain to be identified. Here we report two distinct functions of doublecortin-like kinases, chimeric proteins containing both a microtubule-binding domain and a kinase domain in postmitotic neurons. First, doublecortin-like kinases localize to the distal dendrites and promote their growth by enhancing microtubule bundling. Second, doublecortin-like kinases suppress maturation of synapses through multiple pathways, including reduction of PSD-95 by the kinase domain and suppression of spine structural maturation by the microtubule-binding domain. Thus, doublecortin-like kinases are critical regulators of dendritic development by means of their specific targeting to the distal dendrites, and their local control of dendritic growth and synapse maturation.