- The amyloid precursor protein (APP) and its paralogs, amyloid precursor-like protein 1 (APLP1) and APLP2, are metalloproteins with a putative role both in synaptogenesis and in maintaining synapse structure. Here, we studied the effect of zinc on membrane localization, adhesion, and secretase cleavage of APP, APLP1, and APLP2 in cell culture and rat neurons. For this, we employed live-cell microscopy techniques, a microcontact printing adhesion assay and ELISA for protein detection in cell culture supernatants. We report that zinc induces the multimerization of proteins of the amyloid precursor protein family and enriches them at cellular adhesion sites. Thus, zinc facilitates the formation of de novo APP and APLP1 containing adhesion complexes, whereas it does not have such influence on APLP2. Furthermore, zinc-binding prevented cleavage of APP and APLPs by extracellular secretases. In conclusion, the complexation of zinc modulates neuronal functions of APP and APLPs by (i) regulating formation of adhesion complexes, most prominentlyThe amyloid precursor protein (APP) and its paralogs, amyloid precursor-like protein 1 (APLP1) and APLP2, are metalloproteins with a putative role both in synaptogenesis and in maintaining synapse structure. Here, we studied the effect of zinc on membrane localization, adhesion, and secretase cleavage of APP, APLP1, and APLP2 in cell culture and rat neurons. For this, we employed live-cell microscopy techniques, a microcontact printing adhesion assay and ELISA for protein detection in cell culture supernatants. We report that zinc induces the multimerization of proteins of the amyloid precursor protein family and enriches them at cellular adhesion sites. Thus, zinc facilitates the formation of de novo APP and APLP1 containing adhesion complexes, whereas it does not have such influence on APLP2. Furthermore, zinc-binding prevented cleavage of APP and APLPs by extracellular secretases. In conclusion, the complexation of zinc modulates neuronal functions of APP and APLPs by (i) regulating formation of adhesion complexes, most prominently for APLP1, and (ii) by reducing the concentrations of neurotrophic soluble APP/APLP ectodomains.…
MetadatenAuthor details: | Magnus C. Mayer, Linda Schauenburg, Greta Thompson-Steckel, Valentin DunsingORCiDGND, Daniela Kaden, Philipp Voigt, Michael Schaefer, Salvatore ChiantiaORCiDGND, Timothy E. Kennedy, Gerhard Multhaup |
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DOI: | https://doi.org/10.1111/jnc.13540 |
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ISSN: | 0022-3042 |
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ISSN: | 1471-4159 |
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Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/26801522 |
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Title of parent work (English): | Journal of neurochemistry |
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Publisher: | Wiley-Blackwell |
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Place of publishing: | Hoboken |
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Publication type: | Article |
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Language: | English |
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Year of first publication: | 2016 |
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Publication year: | 2016 |
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Release date: | 2020/03/22 |
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Tag: | amyloid precursor protein; amyloid precursor-like protein; neuronal adhesion; number and brightness; zinc |
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Volume: | 137 |
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Number of pages: | 11 |
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First page: | 266 |
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Last Page: | 276 |
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Funding institution: | DFG [MU901, SFB740, GRK1123, Exc 257 NeuroCure]; German Federal Ministry of Education and Research through the Kompetenznetz Degenerative Demenzen (Forderkennzeichen) [01 GI 1004G]; Canadian Institute of Health Research [MOP-133411, MOP-114965] |
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Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie |
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Peer review: | Referiert |
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