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

Doublecortin-like kinase enhances dendritic remodelling and negatively regulates synapse maturation.
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DOI:
10.1038/ncomms2443
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发表时间:
2013
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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树突形态发生和在适当的树突位置形成突触对于建立适当的神经元连接是必不可少的。最近的影像学研究提供了证据,稳定动态的树突远端分支的新突触的增加。然而,参与树突生长和抑制突触成熟的分子仍有待确定。在这里,我们报告两个不同的功能doublecortin样激酶,嵌合蛋白含有微管结合域和激酶域在有丝分裂后的神经元。首先,doublecortin样激酶定位于远端树突,并通过增强微管集束促进其生长。其次,doublecortin样激酶通过多种途径抑制突触的成熟,包括通过激酶结构域减少PSD-95和通过微管结合结构域抑制棘结构成熟。因此,doublecortin样激酶是树突发育的关键调节因子,通过其特异性靶向远端树突,以及其对树突生长和突触成熟的局部控制。
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.
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