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Downregulation of myosin II‐B by siRNA alters the subcellular localization of APP and increases Aβ deposition in N2a cells
Author(s) -
Ricciarelli Roberta,
Massone Sara,
Argellati Francesca,
Domenicotti Cinzia,
Marinari Umberto Maria,
Pronzato Maria Adelaide
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a18-d
Subject(s) - microbiology and biotechnology , myosin , cytoskeleton , subcellular localization , amyloid precursor protein , biology , transmembrane protein , gene isoform , neuroscience , axoplasmic transport , alzheimer's disease , receptor , biochemistry , cell , cytoplasm , pathology , disease , medicine , gene
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 type I transmembrane protein ubiquitously expressed in the nervous system. Although the proteolytic processing of APP has been implicated in the pathogenesis of AD, the normal function of APP, whether this function is related to the proteolytic processing, and where this processing takes place in neurons remain unknown. APP is anterogradely transported along the axon apparently on cytoskeletal tracks. Moreover, several studies indicate that APP processing may occur within axonal or presinaptic terminals, supporting the hypothesis 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 down‐regulation of myosin II‐B, the major myosin isoform in neurons, is able to increase Aβ secretion, 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. Work funded by grants from COFIN 2004 (no. 2004068928_003 and no. 2004063943_001).