title: BACE1 modulates filopodia-like protrusions induced by sodium channel beta4 subunit.
abstract: Processing of APP by BACE1 plays a crucial role in the pathogenesis of Alzheimer disease (AD). Recently, the voltage-gated sodium channel (Na(v)) beta4 subunit (beta4), an auxiliary subunit of Na(v) 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 beta4 remains illusive. Here, we report the biological effects of beta4 processing by BACE1. Overexpression of beta4 in Neuro2a cells promoted neurite extension and increased the number of F-actin rich filopodia-like protrusions. While coexpression of BACE1 together with beta4 further accelerated neurite extension, the number of filopodia-like protrusions was reduced. Overexpression of C-terminal fragment of beta4 that was generated by BACE1 (beta4-CTF) partially recapitulated the results obtained with BACE1 overexpression. These results suggest that the processing of beta4 by BACE1 regulates neurite length and filopodia-like protrusion density in neurons.
authors.affiliation: Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Haruko
authors.initials: H
authors.lastname: Miyazaki
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Oyama
authors.forename: Hon-Kit
authors.initials: HK
authors.lastname: Wong
authors.forename: Kumi
authors.initials: K
authors.lastname: Kaneko
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakurai
authors.forename: Akira
authors.initials: A
authors.lastname: Tamaoka
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Nukina
mesh_terms: D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D045744:Cell Line, Tumor; D051379:Mice; D008969:Molecular Sequence Data; D016501:Neurites / Q000648:ultrastructure*; D011554:Pseudopodia / Q000648:ultrastructure*; D015222:Sodium Channels / Q000737:chemistry / Q000378:metabolism*; D062585:Voltage-Gated Sodium Channel beta-4 Subunit
chemical_list: C497241:Scn4b protein, mouse; D015222:Sodium Channels; D062585:Voltage-Gated Sodium Channel beta-4 Subunit; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human