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小脑的笔细胞组织在出生后发育过程中需要神经束蛋白在浦肯野细胞和篮状细胞中发挥不同的功能。

Pinceau organization in the cerebellum requires distinct functions of neurofascin in Purkinje and basket neurons during postnatal development.

机构信息

Curriculum in Neurobiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7545, USA.

出版信息

J Neurosci. 2012 Apr 4;32(14):4724-42. doi: 10.1523/JNEUROSCI.5602-11.2012.

Abstract

Basket axon collaterals synapse onto the Purkinje soma/axon initial segment (AIS) area to form specialized structures, the pinceau, which are critical for normal cerebellar function. Mechanistic details of how the pinceau become organized during cerebellar development are poorly understood. Loss of cytoskeletal adaptor protein Ankyrin G (AnkG) results in mislocalization of the cell adhesion molecule Neurofascin (Nfasc) at the Purkinje AIS and abnormal organization of the pinceau. Loss of Nfasc in adult Purkinje neurons leads to slow disorganization of the Purkinje AIS and pinceau morphology. Here, we used mouse conditional knock-out techniques to show that selective loss of Nfasc, specifically in Purkinje neurons during early development, prevented maturation of the AIS and resulted in loss of Purkinje neuron spontaneous activity and pinceau disorganization. Loss of Nfasc in both Purkinje and basket neurons caused abnormal basket axon collateral branching and targeting to Purkinje soma/AIS, leading to extensive pinceau disorganization, Purkinje neuron degeneration, and severe ataxia. Our studies reveal that the Purkinje Nfasc is required for AIS maturation and for maintaining stable contacts between basket axon terminals and the Purkinje AIS during pinceau organization, while the basket neuron Nfasc in combination with Purkinje Nfasc is required for proper basket axon collateral outgrowth and targeting to Purkinje soma/AIS. Thus, cerebellar pinceau organization requires coordinated mechanisms involving specific Nfasc functions in both Purkinje and basket neurons.

摘要

蒲肯野细胞树突分支与浦肯野细胞体/轴突起始段(AIS)区域上的篮状细胞轴突侧支形成特殊结构,即浦肯野细胞刷状结构,对于正常小脑功能至关重要。但是,小脑发育过程中浦肯野细胞刷状结构是如何组织起来的机制细节还知之甚少。细胞骨架衔接蛋白锚蛋白 G(AnkG)缺失导致细胞黏附分子神经束蛋白(Nfasc)在浦肯野细胞 AIS 处定位异常,并导致浦肯野细胞刷状结构异常。成年浦肯野神经元中 Nfasc 的缺失会导致浦肯野细胞 AIS 和浦肯野细胞刷状结构形态的缓慢紊乱。在这里,我们使用小鼠条件性敲除技术表明,早期发育时特异性缺失浦肯野神经元中的 Nfasc,会阻止 AIS 的成熟,并导致浦肯野神经元自发活动和浦肯野细胞刷状结构的丧失。浦肯野神经元和篮状细胞神经元中 Nfasc 的缺失都会导致篮状细胞轴突侧支分支和靶向浦肯野细胞体/AIS 的异常,从而导致广泛的浦肯野细胞刷状结构紊乱、浦肯野神经元退化和严重的共济失调。我们的研究表明,浦肯野细胞 Nfasc 对于 AIS 的成熟以及在浦肯野细胞刷状结构形成过程中维持篮状细胞轴突末梢与浦肯野细胞 AIS 之间的稳定接触是必需的,而篮状细胞神经元 Nfasc 与浦肯野细胞 Nfasc 一起对于适当的篮状细胞轴突侧支的生长和靶向浦肯野细胞体/AIS 是必需的。因此,小脑浦肯野细胞刷状结构的组织需要涉及浦肯野和篮状神经元中特定 Nfasc 功能的协调机制。

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7
Mechanisms and molecules of neuronal wiring: a primer.
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8
A new Kv1.2 channelopathy underlying cerebellar ataxia.
J Biol Chem. 2010 Oct 15;285(42):32160-73. doi: 10.1074/jbc.M110.153676. Epub 2010 Aug 9.
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Building and maintaining the axon initial segment.
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