title: Doublecortin-like kinase enhances dendritic remodelling and negatively regulates synapse maturation.
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.
authors: Department of Cellular Neurobiology, University of Tokyo, Tokyo 113-0033, Japan.
authors: Euikyung
authors: E
authors: Shin
authors: Yutaro
authors: Y
authors: Kashiwagi
authors: Toshihiko
authors: T
authors: Kuriu
authors: Hirohide
authors: H
authors: Iwasaki
authors: Teruyuki
authors: T
authors: Tanaka
authors: Hiroyuki
authors: H
authors: Koizumi
authors: Joseph G
authors: JG
authors: Gleeson
authors: Shigeo
authors: S
authors: Okabe
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003712:Dendrites / Q000201:enzymology*; D049229:Dendritic Spines / Q000201:enzymology; D000089742:Doublecortin-Like Kinases; D019706:Excitatory Postsynaptic Potentials; D055785:Gene Knockdown Techniques; D018698:Glutamic Acid / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D010641:Phenotype; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000201:enzymology; D013569:Synapses / Q000201:enzymology*
chemical_list: D020033:Protein Isoforms; D034741:RNA, Small Interfering; D018091:Receptors, AMPA; D049452:Green Fluorescent Proteins; D018698:Glutamic Acid; D000089742:Doublecortin-Like Kinases; C485525:Dclk1 protein, mouse; C540863:Dclk2 protein, mouse; D017346:Protein Serine-Threonine Kinases
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