Doublecortin-like kinase enhances dendritic remodelling and negatively regulates synapse maturation
| Autor: | Shigeo Okabe, Euikyung Shin, Joseph G. Gleeson, Toshihiko Kuriu, Teruyuki Tanaka, Yutaro Kashiwagi, Hiroyuki Koizumi, Hirohide Iwasaki |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Dendritic Spines
Green Fluorescent Proteins Morphogenesis Glutamic Acid General Physics and Astronomy Protein Serine-Threonine Kinases Biology Hippocampus Article General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences Doublecortin-Like Kinases 0302 clinical medicine Animals Protein Isoforms Receptors AMPA RNA Small Interfering 030304 developmental biology Mice Knockout 0303 health sciences Multidisciplinary Kinase Microtubule bundling Excitatory Postsynaptic Potentials Dendrites General Chemistry Fusion protein Protein Structure Tertiary Cell biology Doublecortin Protein Transport Phenotype Animals Newborn Microscopy Fluorescence nervous system Protein kinase domain Gene Knockdown Techniques Synapses biology.protein A kinase 030217 neurology & neurosurgery Synapse maturation Signal Transduction Subcellular Fractions |
| Zdroj: | Nature communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms2443 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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