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Tetraspanin 3: A central endocytic membrane component regulating the expression of ADAM10, presenilin and the amyloid precursor protein
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SYSNO ASEP 0473058 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Tetraspanin 3: A central endocytic membrane component regulating the expression of ADAM10, presenilin and the amyloid precursor protein Author(s) Seipold, L. (DE)
Damme, M. (DE)
Prox, J. (DE)
Rabe, B. (DE)
Kašpárek, Petr (UMG-J)
Sedláček, Radislav (UMG-J) RID
Altmeppen, H. (DE)
Willem, M. (DE)
Boland, B. (IE)
Glatzel, M. (DE)
Saftig, P. (DE)Number of authors 11 Source Title Biochimica Et Biophysica Acta-Molecular Cell Research. - : Elsevier - ISSN 0167-4889
Roč. 1864, č. 1 (2017), s. 217-230Number of pages 24 s. Language eng - English Country NL - Netherlands Keywords ADAM10 ; Tetraspanin ; APP ; Presenilin Subject RIV EB - Genetics ; Molecular Biology OECD category Biochemistry and molecular biology R&D Projects LM2011032 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LM2015040 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support UMG-J - RVO:68378050 UT WOS 000390514600020 DOI 10.1016/j.bbamcr.2016.11.003 Annotation Despite existing knowledge about the role of the A Disintegrin and Metalloproteinase 10 (ADAM10) as the alpha-secretase involved in the non-amyloidogenic processing of the amyloid precursor protein (APP) and Notch signalling we have only limited information about its regulation. In this study, we have identified ADAM10 interactors using a split ubiquitin yeast two hybrid approach. Tetraspanin 3 (Tspan3), which is highly expressed in the murine brain and elevated in brains of Alzheimer's disease (AD) patients, was identified and confirmed to bind ADAM10 by co-immunoprecipitation experiments in mammalian cells in complex with APP and the gamma-secretase protease presenilin. Tspan3 expression increased the cell surface levels of its interacting partners and was mainly localized in early and late endosomes. In contrast to the previously described ADAM10-binding tetraspanins, Tspan3 did not affect the endoplasmic reticulum to plasma membrane transport of ADAM10. Heterologous Tspan3 expression significantly increased the appearance of carboxy-terminal cleavage products of ADAM10 and APP, whereas N-cadherin ectodomain shedding appeared unaffected. Inhibiting the endocytosis of Tspan3 by mutating a critical cytoplasmic tyrosine-based internalization motif led to increased surface expression of APP and ADAM10. After its downregulation in neuroblastoma cells and in brains of Tspan3-deficient mice, ADAM10 and APP levels appeared unaltered possibly due to a compensatory increase in the expression of Tspans 5 and 7, respectively. In conclusion, our data suggest that Tspan3 acts in concert with other tetraspanins as a stabilizing factor of active ADAM10, APP and the gamma-secretase complex at the plasma membrane and within the endocytic pathway. (C) 2016 Elsevier B.V. All rights reserved. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2017
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