Novel function of PS2V: change in conformation of tau proteins☆
Section snippets
Materials and methods
Cell culture and plasmid transfection. Cell culture and plasmid transfection were performed as previously described [6], [8]. Transfection of expression plasmids was carried out using LipofectAmine (Gibco-BRL). The full-length cDNAs of PS2 and PS2V were amplified by RT-PCR with attached EcoRI and XhoI sites and subcloned into the pcDNA3(+) vector (Invitrogen) between corresponding restriction enzyme sites.
Immunoblotting assays. Immunoblotting was performed as previously described [10], [11]
PS2V changes phosphorylation and conformation of tau proteins
Tau proteins are part of a family of six alternative splice forms, with their molecular weights ranging from 45 to 65 kDa on SDS–PAGE (reviewed in [12]). Further, the phosphorylated forms of the tau proteins are electrophoresed at molecular weights from 55 to 74 kDa (reviewed in [12]). First, we detected anti-tau2 antibody-positive tau proteins, which include all forms of tau, in human neuroblastoma SK-N-SH (Fig. 1A). Then, we examined the effects of PS2V on the expression, phosphorylation, and
Acknowledgements
T.M. is supported by the Japan Science and Technology Agency (JST). The authors gratefully acknowledge Ms. A. Arakawa for her help.
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Aberrant regulation of alternative pre-mRNA splicing in schizophrenia
2010, Neurochemistry InternationalCitation Excerpt :The protein is normal until exon 4, but exon 5 is skipped, causing a frame-shift and the addition of five novel amino acids encoded by exon 6 until a stop codon is reached (Fig. 5A). The PS2V protein increases levels of amyloid-beta (Sato et al., 2001) and causes conformational changes in tau proteins (Nishikawa et al., 2004) by impairing the signaling pathway of the unfolded-protein response in the endoplasmic reticulum in in vitro studies using neuroblastoma cell lines (Sato et al., 2001). The mechanism of this exon skipping has been well researched.
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Abbreviations: AD, Alzheimer’s disease; FTDP-17, frontotemporal dementia with Parkinsonism linked to chromosome 17; HMGA1a, high mobility group protein A1a; NFT, Neurofibrillary tangle; PS2, presenilin-2; PS2V, alternative splice form of PS2 gene that lacks exon 5.
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These authors contributed equally to this work.