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Involvement of myosin II‐B and protein kinase C in the processing of APP
Author(s) -
Ricciarelli Roberta,
Argellati Francesca,
Massone Sara,
Domenicotti Cinzia,
Marengo Barbara,
Pronzato Maria A,
Marinari Umberto M
Publication year - 2008
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.22.2_supplement.585
Subject(s) - microbiology and biotechnology , protein kinase c , amyloid precursor protein , myosin , cytoskeleton , phosphorylation , cytoplasm , kinase , chemistry , biology , alzheimer's disease , biochemistry , cell , medicine , disease
The Alzheimer's disease (AD) brain pathology is characterized by extracellular deposits of amyloid‐β (Aβ) peptides cleaved from the amyloid precursor protein (APP). Although the proteolytic processing of APP has been implicated in the pathogenesis of AD, why and where this processing takes place in neurons remains unknown. Several studies support the hypothesis that APP functions as a vesicular receptor for cytoskeletal motor proteins. Our recent results strongly suggest that the trafficking of APP involves myosin II‐B, important contributor to the cytoskeleton of neuronal cells (Massone et al., Biochem Biophys Res Commun. 2007 vol. 362 pp. 633–8). It is known that activation of protein kinase C (PKC) reduces secretion of Aβ favoring the non‐amyloidogenic processing of APP. PKC phosphorylates myosin II‐B, regulating the assembly of the motor protein and its shuttling between the cell cortex and the cytoplasm. These observations, together with our very recent results, are consistent with a model in which PKC‐mediated phosphorylation of myosin II‐B regulates shuttling of APP between the cell periphery and the perinuclear region, shifting APP away from the compartments where its amyloidogenic processing is favored or, alternatively, moving APP toward a non‐amyloidogenic pathway. Work funded by Fondazione CARIGE (2007.0650‐71) and PRIN (2006065711_002).