Independent regulation of process outgrowth and neuronal connectivity

Posted on March 5, 2013
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

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

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.

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.

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

Source: University of Tokyo