Alkalizing drugs induce accumulation of amyloid precursor protein by-products in luminal vesicles of multivesicular bodies

作者：Vingtdeux Valerie; Hamdane Malika; Loyens Anne; Gele Patrick; Drobeck Herve; Begard Severine; Galas Marie Christine; Delacourte Andre; Beauvillain Jean Claude; Buee Luc; Sergeant Nicolas^*

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282(25): 18197-18205.

DOI：10.1074/jbc.M609475200

Amyloid precursor protein (APP) metabolism is central to the pathogenesis of Alzheimer disease. We showed recently that the amyloid intracellular domain (AICD), which is released by gamma-secretase cleavage of APP C-terminal fragments (CTFs), is strongly increased in cells treated with alkalizing drugs (Vingtdeux, V., Hamdane, M., Begard, S., Loyens, A., Delacourte, A., Beauvillain, J.- C., Buee, L., Marambaud, P., and Sergeant, N. (2007) Neurobiol. Dis. 25, 686-696). Herein, we aimed to determine the cell compartment in which AICD accumulates. We show that APP-CTFs and AICD are present in multivesicular structures. Multivesicular bodies contain intraluminal vesicles (known as exosomes) when released in the extracellular space. We demonstrate that APP, APP-CTFs, and AICD are integrated and secreted within exosomes in differentiated neuroblastoma and primary neuronal culture cells. Together with recent data showing that amyloid-beta is also found in exosomes, our data show that multivesicular bodies are essential organelles for APP metabolism and that all APP metabolites can be secreted in the extracellular space.

• 出版日期2007-6-22
• 单位河北医科大学