Atlastin-1 regulates dendritic morphogenesis in mouse cerebral cortex
Atlastin-1 regulates dendritic morphogenesis in mouse cerebral cortex
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Atlastin-1 调节小鼠大脑皮层树突形态发生
DOI：
10.1016/j.neures.2013.08.007
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发表时间：
2013-11-01
影响因子：
2.9
通讯作者：
Chen, Jie-Guang
中科院分区：
文献类型：
--
作者：
Gao, Ying;Jiang, Tian;Chen, Jie-Guang
遗传性痉挛性截瘫（HSP）是人类遗传性疾病，其特征是下肢痉挛和虚弱。已经在HSP SPG 3A患者中鉴定了atlastin-1（ATLI）的突变。然而，ATLI在哺乳动物脑中的功能仍不清楚。本研究发现，ATLI mRNA在小鼠大脑皮层发育早期的深层表达受到限制。我们通过子宫内电穿孔将其质粒递送到上层皮层神经元来检查ATL 1的功能。在锥体神经元异位表达的影响，确定在培养和原位在出生后阶段的新皮质发育。在培养的皮质神经元中，过表达ATL 1增加了树枝状突起的生长和树枝状化，而缺乏GTPase活性的HSP相关突变体R217 Q则没有这样的作用。与此一致，野生型ATLI的体内表达，但不是突变体R217 Q，增加了皮质神经元的树突状生长。这表明ATL 1对树突状形态发生的作用取决于其GT3活性。ATL 1和R217 Q的表达不影响皮层神经元的迁移。这些结果表明，ATL 1调节树突状细胞的形态发生，这可能为遗传性痉挛性截瘫SPG 3A的神经病理机制提供新的见解。(C)2013 Elsevier爱尔兰有限公司和日本神经科学学会。All rights reserved.
Hereditary spastic paraplegias (HSPs) are human genetic disorders characterized by lower extremity spasticity and weakness. Mutations in atlastin-1 (ATLI) have been identified in patients with HSP SPG3A. However, the function of ATLI in the mammalian brain remains unclear. Here, we found that expression of ATLI mRNA was restricted in the deep layer of mouse cerebral cortex during the early development. We examined ATL1 functions by delivering its plasmids to the upper layer cortical neurons using in utero electroporation. The effects of ectopic expression in the pyramidal neurons were determined both in culture and in situ at postnatal stages of neocortical development. In cultured cortical neurons, over-expressing ATL1 increased dendrite growth and arborization, whereas HSP-associated mutant R217Q which is devoid of GTPase activity, had no such effects. Consistent with this, in vivo expression of wild type ATLI, but not of the mutant R217Q, increased dendritic growth of the cortical neurons. This suggests that the role of ATL1 on dendritic morphogenesis depends on its GTPase activity. The expression of ATL1 and R217Q did not affect the migration of cortical neurons. These results indicate that ATL1 regulates dendritic morphogenesis, which may provide new insights into the neuropathogenic mechanism of hereditary spastic paraplegia SPG3A. (C) 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.