TY - JOUR
T1 - BACE1 modulates filopodia-like protrusions induced by sodium channel β4 subunit
AU - Miyazaki, Haruko
AU - Oyama, Fumitaka
AU - Wong, Hon Kit
AU - Kaneko, Kumi
AU - Sakurai, Takashi
AU - Tamaoka, Akira
AU - Nukina, Nobuyuki
N1 - Funding Information:
We thank Dr. A. Miyawaki (RIKEN Brain Science Institute) for providing Venus cDNA, M. Kumai (Research Resource Center, RIKEN Brain Science Institute) for antibody preparation. This work was supported in part by Grants-in-Aid for Scientific Research 18500284, Grants-in-Aid for Scientific Research on Priority Areas 17025044 from the Ministry of Education, Culture, Sports, Science, and Technology, Japan and Grants-in-Aid from the Ministry of Health, Labor, and Welfare. HM was supported by the Junior Research Associate Program in RIKEN.
PY - 2007/9/14
Y1 - 2007/9/14
N2 - Processing of APP by BACE1 plays a crucial role in the pathogenesis of Alzheimer disease (AD). Recently, the voltage-gated sodium channel (Nav) β4 subunit (β4), 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 β4 remains illusive. Here, we report the biological effects of β4 processing by BACE1. Overexpression of β4 in Neuro2a cells promoted neurite extension and increased the number of F-actin rich filopodia-like protrusions. While coexpression of BACE1 together with β4 further accelerated neurite extension, the number of filopodia-like protrusions was reduced. Overexpression of C-terminal fragment of β4 that was generated by BACE1 (β4-CTF) partially recapitulated the results obtained with BACE1 overexpression. These results suggest that the processing of β4 by BACE1 regulates neurite length and filopodia-like protrusion density in neurons.
AB - Processing of APP by BACE1 plays a crucial role in the pathogenesis of Alzheimer disease (AD). Recently, the voltage-gated sodium channel (Nav) β4 subunit (β4), 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 β4 remains illusive. Here, we report the biological effects of β4 processing by BACE1. Overexpression of β4 in Neuro2a cells promoted neurite extension and increased the number of F-actin rich filopodia-like protrusions. While coexpression of BACE1 together with β4 further accelerated neurite extension, the number of filopodia-like protrusions was reduced. Overexpression of C-terminal fragment of β4 that was generated by BACE1 (β4-CTF) partially recapitulated the results obtained with BACE1 overexpression. These results suggest that the processing of β4 by BACE1 regulates neurite length and filopodia-like protrusion density in neurons.
KW - BACE1
KW - Filopodia-like protrusion
KW - Neurite outgrowth
KW - Sodium channel β4 subunit
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U2 - 10.1016/j.bbrc.2007.06.170
DO - 10.1016/j.bbrc.2007.06.170
M3 - Article
C2 - 17644063
AN - SCOPUS:34547110808
SN - 0006-291X
VL - 361
SP - 43
EP - 48
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -