Abstract
Using a yeast two-hybrid system, we screened a human brain cDNA library for possible interacting proteins with the C-terminal cytosolic tail of the beta-secretase beta-amyloid protein converting enzyme (BACE)1. This identified seven potential candidates, including the brain-specific type II membrane protein BRI3. Co-localization and co-immunoprecipitation experiments confirmed that BACE1 and BRI3 co-localize and interact with each other via the cytosolic tail of BACE1. Furthermore, pulse and pulse-chase analyses revealed that the pro-protein convertases furin, and to a lesser extent PC7 and PC5A, process BRI3 into a C-terminal secreted approximately 4-kDa product. Thus, furin efficiently processes both pro-BACE1 and its novel interacting protein pro-BRI3.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amino Acid Sequence
-
Amyloid Precursor Protein Secretases
-
Amyloid beta-Peptides / metabolism*
-
Animals
-
Aspartic Acid Endopeptidases / genetics
-
Aspartic Acid Endopeptidases / metabolism*
-
Brain / metabolism
-
Cell Line
-
Endopeptidases
-
Furin / metabolism*
-
Humans
-
Membrane Proteins / genetics
-
Membrane Proteins / metabolism*
-
Mice
-
Mice, Transgenic
-
Molecular Sequence Data
-
Nerve Tissue Proteins
-
Protein Binding / physiology
-
Protein Interaction Mapping
-
Protein Processing, Post-Translational*
-
Transfection
Substances
-
Amyloid beta-Peptides
-
BRI3 protein, human
-
Membrane Proteins
-
Nerve Tissue Proteins
-
Amyloid Precursor Protein Secretases
-
Endopeptidases
-
Furin
-
Aspartic Acid Endopeptidases
-
BACE1 protein, human
-
Bace1 protein, mouse