Non-proteolytic effect of β-site APP-cleaving enzyme 1 (BACE1) on sodium channel function

被引：38

作者：

Huth, Tobias ^{[1
]}

Schmidt-Neuenfeldt, Karoline ^{[1
]}

Rittger, Andrea

Saftig, Paul

Reiss, Karina

Alzheimer, Christian ^{[1
]}

机构：

[1] Univ Kiel, Inst Physiol, D-24098 Kiel, Germany

来源：

NEUROBIOLOGY OF DISEASE | 2009年 / 33卷 / 02期

关键词：

BACE1; Alzheimer's disease; Neuronal excitability; Sodium channels; Nav1.2 alpha subunit; beta 2 and beta 4-subunits; Patch-clamp recordings; Protein interactions; CELL-ADHESION; SUBUNITS; GLYCOPROTEIN; PRESENILINS; SEIZURES;

D O I：

10.1016/j.nbd.2008.10.015

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The beta-site APP-cleaving enzyme 1 (BACE1) is widely known for its pivotal role in the amyloidogenic pathway leading to Alzheimer's disease. Here, we elaborate on the recent finding that auxiliary subunits of voltage-gated sodium channels (beta 2 and beta 4) are BACE substrates. BACE1 produced complex effects on sodium channel gating that could be only partially explained by beta 2/beta 4 cleavage. To characterize the unexpected non-proteolytic effect of BACE1, we examined HEK cells co-transfected with only Nav1.2 and either normal or catalytically inactive BACE1. Both BACE1 variants produced virtually identical effects on sodium channel gating, which would lead to enhanced cellular excitability. The non-proteolytic BACE1 effect on Nav1.2 current was confirmed in murine neuroblastoma cells, which express sodium channels endogenously, but lack beta 2 and beta 4. Our study reveals an important facet of BACE1 function that should help to decipher the role of BACE1 in normal and demented brain. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：282 / 289

页数：8

共 25 条

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