Lamin B1 protein is required for dendrite development in primary mouse cortical neurons.
Lamin B1 protein is required for dendrite development in primary mouse cortical neurons.
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DOI：
10.1091/mbc.e15-05-0307
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发表时间：
2016-01-01
影响因子：
3.3
通讯作者：
Gasparini L
中科院分区：
文献类型：
--
作者：
Giacomini C;Mahajani S;Ruffilli R;Marotta R;Gasparini L
核纤层蛋白 B1 缺失会对大脑发育产生不利影响。 Lamin B1 功能丧失会影响原代小鼠皮质神经元的神经元发育，严重损害树突长度和复杂性。这种有缺陷的树突发育源于核 ERK 信号传导受损，并且可能是核孔的错误定位。核纤层蛋白 B1 是核层的关键组成部分，在大脑发育和功能中发挥着重要作用。人类核纤层蛋白 B1 (LMNB1) 基因的重复与成人发病的常染色体显性脑白质营养不良有关，小鼠和人类核纤层蛋白 B1 的功能丧失突变是神经管缺陷的易感因素。在小鼠中，内源性核纤层蛋白 B1 (Lmnb1) 的实验性消融会严重损害胚胎皮质生成。在这里，我们报告，在原代小鼠皮质神经元中，LMNB1 过度表达会减少轴突生长，而内源性 Lmnb1 缺乏会导致树突发育异常。在缺乏 Lmnb1 的情况下，树突的长度和复杂性都会降低，并且它们的生长对 KCl 刺激没有反应。这种有缺陷的树突生长源于 ERK 信号传导受损。在 Lmnb1 缺失神经元中，ERK 被正确磷酸化，但磷酸化 ERK 未能转位至细胞核，这可能是由于核膜上的核孔复合物 (NPC) 离域所致。总而言之，这些数据强调了核纤层蛋白 B1 通过调节特定信号分子的核穿梭和 NPC 分布，在小鼠皮质神经元树突发育中发挥着以前未被认识的作用。
Lamin B1 depletion has detrimental effects on brain development. Lamin B1 loss of function affects neuronal development in primary mouse cortical neurons, strongly impairing dendrite length and complexity. This defective dendrite development stems from impaired nuclear ERK signaling and, possibly, mislocalization of nuclear pores. Lamin B1, a key component of the nuclear lamina, plays an important role in brain development and function. A duplication of the human lamin B1 (LMNB1) gene has been linked to adult-onset autosomal dominant leukodystrophy, and mouse and human loss-of-function mutations in lamin B1 are susceptibility factors for neural tube defects. In the mouse, experimental ablation of endogenous lamin B1 (Lmnb1) severely impairs embryonic corticogenesis. Here we report that in primary mouse cortical neurons, LMNB1 overexpression reduces axonal outgrowth, whereas deficiency of endogenous Lmnb1 results in aberrant dendritic development. In the absence of Lmnb1, both the length and complexity of dendrites are reduced, and their growth is unresponsive to KCl stimulation. This defective dendritic outgrowth stems from impaired ERK signaling. In Lmnb1-null neurons, ERK is correctly phosphorylated, but phospho-ERK fails to translocate to the nucleus, possibly due to delocalization of nuclear pore complexes (NPCs) at the nuclear envelope. Taken together, these data highlight a previously unrecognized role of lamin B1 in dendrite development of mouse cortical neurons through regulation of nuclear shuttling of specific signaling molecules and NPC distribution.