title: NACP, a synaptic protein involved in Alzheimer's disease, is differentially regulated during megakaryocyte differentiation.
abstract: Non-amyloid-beta component precursor (NACP) is a presynaptic protein which may play a role in amyloidogenesis in Alzheimer's disease (AD). Since an abnormal function of platelets has been demonstrated in AD, platelets could be used as a model to investigate the role of NACP in this disease. We characterized the patterns of NACP and beta-synuclein expression in a megakaryocyte-platelet system (K562). In this hematopoietic cell line, NACP expression was up-regulated during phorbol ester-induced megakaryocytic differentiation, while beta-synuclein was down-regulated. Consistent with this, NACP but not beta-synuclein was abundantly expressed in platelets. Immunogold electron microscopy of platelets showed that NACP is loosely associated with the plasma membrane, the endomembrane system and, occasionally, with the membrane of secretory alpha-granules. These findings suggest that coordinate expression of the synuclein family members may play a critical role during hematopoietic cell differentiation. Additionally, expression of the synuclein family members may be developmentally regulated during neural differentiation.
authors.affiliation: Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla 92093-0624, USA.
authors.forename: M
authors.initials: M
authors.lastname: Hashimoto
authors.forename: M
authors.initials: M
authors.lastname: Yoshimoto
authors.forename: A
authors.initials: A
authors.lastname: Sisk
authors.forename: L J
authors.initials: LJ
authors.lastname: Hsu
authors.forename: M
authors.initials: M
authors.lastname: Sundsmo
authors.forename: A
authors.initials: A
authors.lastname: Kittel
authors.forename: T
authors.initials: T
authors.lastname: Saitoh
authors.forename: A
authors.initials: A
authors.lastname: Miller
authors.forename: E
authors.initials: E
authors.lastname: Masliah
mesh_terms: D000682:Amyloid / Q000096:biosynthesis*; D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D016466:CHO Cells; D002454:Cell Differentiation / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D006224:Cricetinae; D003594:Cytoplasmic Granules / Q000378:metabolism / Q000648:ultrastructure; D017931:DNA Primers; D005786:Gene Expression Regulation; D006801:Humans; D007700:Kinetics; D008533:Megakaryocytes / Q000166:cytology* / Q000378:metabolism; D016253:Microscopy, Immunoelectron; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D016366:Open Reading Frames; D016133:Polymerase Chain Reaction; D011498:Protein Precursors / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000096:biosynthesis; D051843:Synucleins; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured; D051846:beta-Synuclein
chemical_list: D000682:Amyloid; D017931:DNA Primers; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D011994:Recombinant Proteins; C497607:SNCB protein, human; D051843:Synucleins; D051846:beta-Synuclein; D013755:Tetradecanoylphorbol Acetate