β‐Amyloid protein converting enzyme 1 and brain‐specific type II membrane protein BRI3: binding partners processed by furin

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 β‐secretase β‐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 ∼ 4‐kDa product. Thus, furin efficiently processes both pro‐BACE1 and its novel interacting protein pro‐BRI3.