BACE1 interacts with lipid raft proteins.
A neuropathological hallmark of Alzheimer's disease is the presence of amyloid plaques in the brain. Amyloid-beta peptide (Abeta) is the major constituent of the plaques and is generated by proteolytic cleavages of amyloid precursor protein (APP) by beta- and gamma-secretases. Growing evidence shows that lipid rafts are critically involved in regulating the Abeta generation. In support of this, APP, Abeta, and presenilins have been found in lipid rafts. Although cholesterol plays a crucial role in maintaining lipid rafts, functions of other components in the generation of Abeta are unknown. Caveolins (CAVs) and flotillins (FLOTs) are principal proteins related to lipid rafts and have been suggested to be involved in APP processing. Here, we report that FLOT-1 binds to BACE1 (beta-site APP cleaving enzyme 1) and that overexpression of CAV-1 or FLOT-1 results in recruiting BACE1 into lipid rafts and influence on beta-secretase activity in cultured cells. Our results show that both CAV-1 and FLOT-1 may modulate beta-secretase activity by interacting with BACE1.
Hattori
Chinatsu
C
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan.
Asai
Masashi
M
Onishi
Hayato
H
Sasagawa
Noboru
N
Hashimoto
Yasuhiro
Y
Saido
Takaomi C
TC
Maruyama
Kei
K
Mizutani
Shigehiko
S
Ishiura
Shoichi
S
D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases; D015152:Blotting, Northern; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D021962:Membrane Microdomains / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013347:Subcellular Fractions / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; C495540:CAV1 protein, human; D051242:Caveolin 1; D008565:Membrane Proteins; D012333:RNA, Messenger; C106354:flotillins; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human