Heat-shock induces abnormalities in the cellular distribution of amyloid precursor protein (APP) and APP fusion proteins.
The heat shock or stress response may play a role in the pathogenesis of Alzheimer's disease. We conducted experiments to visualize microscopically the distribution of wild type amyloid precursor protein (APP) and the behavior of an APP deletion mutant under stress. This was achieved by heat-shock treatment of cells expressing fusion recombinant APP proteins tagged with secreted placental alkaline phosphatase (SEAP). The fusion proteins were cleaved and secreted in a manner similar to wild type APP in unstressed control cells. SEAP activity was detected by cytochemical methods within the cytoplasm in less than 10% of transfected unstressed cells. Heat shocked cells showed a striking difference from the control cells in that over 90% of the stressed cells displayed strong intracytoplasmic SEAP activity occurring with Golgi-like pattern and/or membranous distribution. The effects of heat shock were not due to a peculiar behavior of the clones and depended on the APP portion of the constructs. This study shows miscompartmentalization of APP under stress. Such cellular changes may bear important implications in the processing of APP.
Pappolla
M A
MA
University of Texas Medical School, Department of Pathology, Houston 77030, USA.
Sambamurti
K
K
Efthimiopoulos
S
S
Refolo
L
L
Omar
R A
RA
Robakis
N K
NK
D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D006651:Histocytochemistry; D006358:Hot Temperature; D010920:Placenta / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D012769:Shock / Q000378:metabolism* / Q000473:pathology*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D016564:Amyloid beta-Protein Precursor; D011993:Recombinant Fusion Proteins; D000469:Alkaline Phosphatase