2005年5月
The low density lipoprotein receptor-related protein (LRP) is a novel beta-secretase (BACE1) substrate
JOURNAL OF BIOLOGICAL CHEMISTRY
- 巻
- 280
- 号
- 18
- 開始ページ
- 17777
- 終了ページ
- 17785
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1074/jbc.M414248200
- 出版者・発行元
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
BACE is a transmembrane protease with beta-secretase activity that cleaves the amyloid precursor protein (APP). After BACE cleavage, APP becomes a substrate for gamma-secretase, leading to release of amyloid-beta peptide (A beta), which accumulates in senile plaques in Alzheimer disease. APP and BACE are co-internalized from the cell surface to early endosomes. APP is also known to interact at the cell surface and be internalized by the low density lipoprotein receptor-related protein (LRP), a multifunctional endocytic and signaling receptor. Using a new fluorescence resonance energy transfer ( FRET)based assay of protein proximity, fluorescence lifetime imaging (FLIM), and co-immunoprecipitation we demonstrate that the light chain of LRP interacts with BACE on the cell surface in association with lipid rafts. Surprisingly, the BACE-LRP interaction leads to an increase in LRP C-terminal fragment, release of secreted LRP in the media and subsequent release of the LRP intracellular domain from the membrane. Taken together, these data suggest that there is a close interaction between BACE and LRP on the cell surface, and that LRP is a novel BACE substrate.
- リンク情報
- ID情報
-
- DOI : 10.1074/jbc.M414248200
- ISSN : 0021-9258
- eISSN : 1083-351X
- PubMed ID : 15749709
- Web of Science ID : WOS:000228807200028