βIII spectrin controls the planarity of Purkinje cell dendrites by modulating perpendicular axon-dendrite interactions
βIII spectrin controls the planarity of Purkinje cell dendrites by modulating perpendicular axon-dendrite interactions
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DOI：
10.1242/dev.194530
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发表时间：
2020-12-01
期刊：
影响因子：
4.6
通讯作者：
Kengaku, Mineko
中科院分区：
文献类型：
--
作者：
Fujishima, Kazuto;Kurisu, Junko;Kengaku, Mineko
轴突和树突布线的几何图案的机制仍然难以捉摸，尽管它在功能性神经回路的形成至关重要。小脑浦肯野细胞（PC）树枝状突起为典型的平面树突，与颗粒细胞（GC）轴突形成正交网络。通过使用静电纺丝的基底，我们再现了PC树突和GC轴突之间的垂直接触在文化。在模型系统中，PC树突显示出垂直于对齐的GC轴突生长的偏好，这可能有助于在体内的平面树突树枝化。我们表明，β III血影蛋白，脊髓小脑共济失调5型的致病蛋白，是需要偏向生长的树突。β III血影蛋白缺乏导致肌动蛋白错误定位和树突状突起中的过度微管侵入，导致异常定向的分支形成。此外，疾病相关突变影响β III血影蛋白控制树突取向的能力。这些数据表明β III血影蛋白组织小鼠树突细胞骨架，从而调节树突相对于传入轴突的定向生长。
The mechanism underlying the geometrical patterning of axon and dendrite wiring remains elusive, despite its crucial importance in the formation of functional neural circuits. The cerebellar Purkinje cell (PC) arborizes a typical planar dendrite, which forms an orthogonal network with granule cell (GC) axons. By using electrospun nanofiber substrates, we reproduce the perpendicular contacts between PC dendrites and GC axons in culture. In the model system, PC dendrites show a preference to grow perpendicularly to aligned GC axons, which presumably contribute to the planar dendrite arborization in vivo. We show that beta III spectrin, a causal protein for spinocerebellar ataxia type 5, is required for the biased growth of dendrites. beta III spectrin deficiency causes actin mislocalization and excessive microtubule invasion in dendritic protrusions, resulting in abnormally oriented branch formation. Furthermore, disease-associated mutations affect the ability of beta III spectrin to control dendrite orientation. These data indicate that beta III spectrin organizes the mouse dendritic cytoskeleton and thereby regulates the oriented growth of dendrites with respect to the afferent axons.