Downregulation of myosin II-B by siRNA alters the subcellular localization of the amyloid precursor protein and increases amyloid-β deposition in N2a cells
- 作者：Sara Massone ; Francesca Argellati ; Mario Passalacqua ; Andrea Armirotti ; Luca Melone ; Cristina d’ ; Abramo ; Umberto M. Marinari ; Cinzia Domenicotti ; Maria A. Pronzato ; Roberta Ricciarelli
- 关键词：Alzheimer’ ; s disease ; Amyloid precursor protein (APP) ; Amyloid-β ; Myosin II
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2007
- 期刊代码：159_0006291x
- 类别：bio
- 出版时间：26 October 2007
- 卷：362
- 期：3
- 页码：633-638
- 文件大小：477 K
摘要
The Alzheimer’s disease (AD) brain pathology is characterized by extracellular deposits of amyloid-β (Aβ) peptides and intraneuronal fibrillar structures. These pathological features may be functionally linked, but the mechanism by which Aβ accumulation relates to neuronal degeneration is still poorly understood. Aβ peptides are fragments cleaved from the amyloid precursor protein (APP), a transmembrane protein ubiquitously expressed in the nervous system. Although the proteolytic processing of APP has been implicated in AD, the physiological function of APP and the subcellular site of APP cleavages remain unknown. The overall structure of the protein and its fast anterograde transport along the axon support the idea that APP functions as a vesicular receptor for cytoskeletal motor proteins.
In the current study, we test the hypothesis that myosin II, important contributor to the cytoskeleton of neuronal cells, may influence the trafficking and/or the processing of APP. Our results demonstrate that downregulation of myosin II-B, the major myosin isoform in neurons, is able to increase Aβ deposition, concomitantly altering the subcellular localization of APP. These new insights might be important for the understanding of the function of APP and provide a novel conceptual framework in which to analyze its pathological role.