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

Euikyung Shin, Yutaro Kashiwagi, Toshihiko Kuriu, Hirohide Iwasaki, Teruyuki Tanaka, Hiroyuki Koizumi, Joseph G. Gleeson and Shigeo Okabe ()
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Euikyung Shin: University of Tokyo
Yutaro Kashiwagi: University of Tokyo
Toshihiko Kuriu: Kagawa School of Pharmaceutical Sciences, University of Tokushima Bunri
Hirohide Iwasaki: University of Tokyo
Teruyuki Tanaka: Graduate School of Medicine, University of Tokyo
Hiroyuki Koizumi: Neurogenetics Laboratory, Howard Hughes Medical Institute, University of California San Diego
Joseph G. Gleeson: Neurogenetics Laboratory, Howard Hughes Medical Institute, University of California San Diego
Shigeo Okabe: University of Tokyo

Nature Communications, 2013, vol. 4, issue 1, 1-14

Abstract: Abstract 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.

Date: 2013
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DOI: 10.1038/ncomms2443

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