CD74 interacts with APP and suppresses the production of Abeta.
BACKGROUND
Alzheimer disease (AD) is characterized by senile plaques, which are mainly composed of beta amyloid (Abeta) peptides. Abeta is cleaved off from amyloid precursor protein (APP) with consecutive proteolytic processing by beta-secretase and gamma-secretase.


RESULTS
Here, we show that CD74, the invariant chain of class II major histocompatibility complex, interacts with APP and serves as a negative regulator of Abeta. CD74 resembles other APP interacters such as BRI2 and BRI3, since all of them reduce the level of Abeta. However, unlike BRIs, CD74 does not reduce the secretion of sAPPalpha or sAPPbeta. Interestingly, in HeLa cells, over expression of CD74 steers APP, but not Notch, to large vacuoles created by CD74.


CONCLUSIONS
Taken together, we propose that CD74 inhibits Abeta production by interacting with and derailing normal trafficking of APP.
Albert Einstein College of Medicine, Department of Microbiology & Immunology, 1300 Morris Park Avenue, Bronx, NY 10461, USA. ldadamio@aecom.yu.edu.
Shuji
S
Matsuda
Yukiko
Y
Matsuda
Luciano
L
D'Adamio