BACE1 modulates filopodia-like protrusions induced by sodium channel β4 subunit
BACE1 modulates filopodia-like protrusions induced by sodium channel β4 subunit
复制标题
DOI：
10.1016/j.bbrc.2007.06.170
复制
发表时间：
2007-09-14
影响因子：
3.1
通讯作者：
Nukina, Nobuyuki
中科院分区：
文献类型：
--
作者：
Miyazaki, Haruko;Oyama, Fumitaka;Nukina, Nobuyuki
BACE 1对APP的加工在阿尔茨海默病（Alzheimer disease，AD）的发病机制中起着至关重要的作用。最近，电压门控钠通道（Na-v）β（4）亚基（beta（4）），即Nav的辅助亚基，被认为是细胞粘附分子，已被鉴定为BACE 1的底物。然而，BACE 1处理β 4的生物学后果仍然是虚幻的。在这里，我们报告了BACE 1对β 4加工的生物学效应。在Neuro 2a细胞中，β 4的过表达促进了神经突的延伸，并增加了富含F-肌动蛋白的丝状伪足样突起的数量。虽然BACE 1与β 4的共表达进一步加速了神经突的延伸，但丝状伪足样突起的数量减少了。由BACE 1产生的β（4）的C-末端片段（β（4）-CTF）的过表达部分地概括了由BACE 1过表达获得的结果。这些结果表明，BACE 1对β 4的加工调节神经元中的神经突长度和丝状伪足样突起密度。(c)2007年爱思唯尔公司All rights reserved.
Processing of APP by BACE1 plays a crucial role in the pathogenesis of Alzheimer disease (AD). Recently, the voltage-gated sodium channel (Na-v) beta(4) subunit (beta(4)), an auxiliary subunit of Nav that is supposed to serve as a cell adhesion molecule, has been identified as a substrate for BACE1. However, the biological consequence of BACE1 processing of beta 4 remains illusive. Here, we report the biological effects of beta(4) processing by BACE1 Overexpression of beta 4 in Neuro2a cells promoted neurite extension and increased the number of F-actin rich filopodia-like protrusions. While coexpression of BACE1 together with beta(4) further accelerated neurite extension, the number of filopodia-like protrusions was reduced. Overexpression of C-terminal fragment of beta(4) that was generated by BACE1 (beta(4)-CTF) partially recapitulated the results obtained with BACE1 overexpression. These results suggest that the processing of beta(4) by BACE1 regulates neurite length and filopodia-like protrusion density in neurons. (c) 2007 Elsevier Inc. All rights reserved.