BACE1 modulates filopodia-like protrusions induced by sodium channel β4 subunit

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.