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

Nat Commun. 2013;4:1440. doi: 10.1038/ncomms2443.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Dendrites / enzymology*
  • Dendritic Spines / enzymology
  • Excitatory Postsynaptic Potentials
  • Gene Knockdown Techniques
  • Glutamic Acid / metabolism
  • Green Fluorescent Proteins / metabolism
  • Hippocampus / cytology
  • Mice
  • Mice, Knockout
  • Microscopy, Fluorescence
  • Phenotype
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary
  • Protein Transport
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA, Small Interfering / metabolism
  • Receptors, AMPA / metabolism
  • Signal Transduction
  • Subcellular Fractions / enzymology
  • Synapses / enzymology*

Substances

  • Protein Isoforms
  • RNA, Small Interfering
  • Receptors, AMPA
  • Green Fluorescent Proteins
  • Glutamic Acid
  • Dcamkl1 protein, mouse
  • Dclk2 protein, mouse
  • Protein-Serine-Threonine Kinases