title: Stabilization of intracellular trafficking and metabolism of amyloid β-protein precursor and Alcadein β by apolipoprotein E.
abstract: Intracellular metabolism of amyloid β-protein precursor (APP) is important for the pathogenesis of Alzheimer's disease (AD). Alcadeins (Alcα, Alcβ, and Alcγ) are neural membrane proteins similar to APP in their localization, metabolism, and cellular function. Isoform ε4 of apolipoprotein E (ApoE) is a major risk factor for AD. We found that ApoE expression attenuated intracellular trafficking of APP and Alcβ, resulting in metabolic stabilization of both proteins. By contrast, Alcα intracellular proteolysis was facilitated by ApoE expression, which was not due to an increase in the primary cleavage of Alcα. This difference may result from binding of ApoE to membrane proteins.
authors.affiliation: Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Ayano
authors.initials: A
authors.lastname: Kimura
authors.affiliation: Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Hata
authors.affiliation: Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan. Electronic address: tsuzuki@pharm.hokudai.ac.jp.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D055550:Protein Stability; D021381:Protein Transport; D059748:Proteolysis
chemical_list: D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; C503225:CLSTN1 protein, human; C472553:CLSTN3 protein, human; D002135:Calcium-Binding Proteins; D008565:Membrane Proteins
keywords: Alcadein; Alzheimer’s disease; Amyloid β-protein precursor; Apolipoprotein E