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Independent regulation of process outgrowth and neuronal connectivity

New roles of cytoskeleton regulator DCLK identified

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Graduate School of Medicine / Faculty of Medicine
2013/02/27

Dendritic morphogenesis and synapse formation at appropriate dendritic locations are essential for establishing proper neuronal connectivity. Recent imaging studies have provided evidence for the stabilization of dynamic distal branches of dendrites by addition of new synapses. However, the molecules involved in both dendritic growth and suppression of synapse maturation remain to be identified.

Neural network formation is driven by the extension of two types of neuronal processes, axons and dendrites, together with differentiation of synapses between these two types of processes. © Shigeo Okabe
DCLK proteins accumulate at the distal ends of dendrites and facilitate their growth. DCLK proteins are also involved in inhibition of synapse formation and maturation, thereby keeping the distal ends of dendrites more dynamic.

A research group lead by Prof. Shigeo Okabe at the University of Tokyo’s Graduate School of Medicine has identified two distinct functions of doublecortin-like kinases (DCLKs), chimeric proteins containing both a microtubule-binding domain and a kinase domain and that are present in postmitotic neurons. First, DCLKs preferentially localize at distal dendrites and promote dendrite growth via their unique microtubule-binding motifs in the N-terminal segment. Second, DCLKs suppress maturation of glutamatergic synapses through multiple pathways, including reduction of a major postsynaptic density protein PSD-95 via the kinase domain and suppression of spine structural maturation via the microtubule-binding domain. These findings indicate that DCLKs are strategically localized to distal dendrites in order to achieve enhancement of process outgrowth and suppression of synapse maturation, both of which are important in maintaining structural plasticity of dendrites.

Press release [PDF] (Japanese)

Paper

Euikyung Shin, Yutaro Kashiwagi, Toshihiko Kuriu, Hirohide Iwasaki, Teruyuki Tanaka, Hiroyuki Koizumi, Joseph G Gleeson, and Shigeo Okabe,
“Doublecortin-like kinase enhances dendritic remodeling and negatively regulates synapse maturation”,
Nature Communications Online Edition: 2012/02/05 (Japan time), doi: 10.1038/ncomms2443.
Article link

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Graduate School of Medicine

Department of Cellular Neurobiology

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