World Alzheimer Conference 2000: Nearing Home BACE?
17 July 2000. There were a number of oral and poster presentations
relating to BACE biology (abstracts 313, 504, 540, 1013, 1269 and
1272). As with the original descriptions of BACE, the reports
presented at this meeting were in broad agreement. Undoubtedly the most
noteworthy presentation was by Martin Citron, but for convenience I have
synthesized the findings of a number groups and listed them below.
BACE is expressed on the cell surface, but undergoes N-terminal
processing and glycosylation in the Golgi and accumulates in endosomes.
Active site-directed mutagenesis (at Asp 93 or Asp289) did not alter
pro-peptide cleavage of BACE indicating that this is not an
Pro-peptide cleavage appears to be mediated by Furin as active BACE
is not produced in Furin-deficient cells, but can be induced by
transfection of such cells with Furin.
BACE is N-glycosylated at three of four possible sites.
BACE contains three intramolecular disulfide bonds between the Cys pairs:
330-380, 278-443 and 216-420. Disruption of any of the three disulfides
results in a loss of enzymatic activity indicating that all three
bridges play a critical role in maintaining the required 3D