Splice variants of the β-site APP-cleaving enzyme BACE1 in human brain and pancreas ☆

Abstract BACE is the β-secretase responsible for the first step in amyloidogenic processing of the amyloid precursor proteinAPP. We have identified two BACE isoforms, BACE1B and BACE1C, lacking 25 and 44 amino acids, respectively. Whereas the BACE1B transcript is present in human pancreasand brain, the BACE1C transcript is found in pancreasonly. In transfected cells both BACE1A, which encodes the originally described full-length BACE1protein and the close homolog BACE2 localized mainly to post- Golgi membranes. In contrast, the two shorter isoforms were found in the endoplasmic reticulum only, and they did not display β-secretase activity. Using RNase protection we in addition show that the major pancreatic transcript is BACE1A. This suggests that the known absence of β-secretase activity in the pancreasis not due to a missing BACE1A transcript.