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Bridging of membrane surfaces by annexin A2
The protein-mediated formation of membrane contacts is a crucial event in many cellular processes ranging from the establishment of organelle contacts to the docking of vesicles to a target membrane. Annexins are Ca(2+) regulated membrane-binding proteins implicated in providing such membrane contac...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168566/ https://www.ncbi.nlm.nih.gov/pubmed/30279443 http://dx.doi.org/10.1038/s41598-018-33044-3 |
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author | Grill, David Matos, Anna L. L. de Vries, Wilke C. Kudruk, Sergej Heflik, Milena Dörner, Wolfgang Mootz, Henning D. Jan Ravoo, Bart Galla, Hans-Joachim Gerke, Volker |
author_facet | Grill, David Matos, Anna L. L. de Vries, Wilke C. Kudruk, Sergej Heflik, Milena Dörner, Wolfgang Mootz, Henning D. Jan Ravoo, Bart Galla, Hans-Joachim Gerke, Volker |
author_sort | Grill, David |
collection | PubMed |
description | The protein-mediated formation of membrane contacts is a crucial event in many cellular processes ranging from the establishment of organelle contacts to the docking of vesicles to a target membrane. Annexins are Ca(2+) regulated membrane-binding proteins implicated in providing such membrane contacts; however, the molecular basis of membrane bridging by annexins is not fully understood. We addressed this central question using annexin A2 (AnxA2) that functions in secretory vesicle exocytosis possibly by providing membrane bridges. By quantitatively analyzing membrane contact formation using a novel assay based on quartz crystal microbalance recordings, we show that monomeric AnxA2 can bridge membrane surfaces Ca(2+) dependently. However, this activity depends on an oxidative crosslink involving a cysteine residue in the N-terminal domain and thus formation of disulfide-linked dimers. Alkylated AnxA2 in which this cysteine residue has been modified and AnxA2 mutants lacking the N-terminal domain are not capable of bridging membrane surfaces. In contrast, a heterotetrameric complex comprising two membrane binding AnxA2 subunits linked by a S100A10 dimer can provide membrane contacts irrespective of oxidation status. Thus, monomeric AnxA2 only contains one lipid binding site and AnxA2-mediated linking of membrane surfaces under non-oxidative intracellular conditions most likely requires AnxA2-S100 complex formation. |
format | Online Article Text |
id | pubmed-6168566 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61685662018-10-05 Bridging of membrane surfaces by annexin A2 Grill, David Matos, Anna L. L. de Vries, Wilke C. Kudruk, Sergej Heflik, Milena Dörner, Wolfgang Mootz, Henning D. Jan Ravoo, Bart Galla, Hans-Joachim Gerke, Volker Sci Rep Article The protein-mediated formation of membrane contacts is a crucial event in many cellular processes ranging from the establishment of organelle contacts to the docking of vesicles to a target membrane. Annexins are Ca(2+) regulated membrane-binding proteins implicated in providing such membrane contacts; however, the molecular basis of membrane bridging by annexins is not fully understood. We addressed this central question using annexin A2 (AnxA2) that functions in secretory vesicle exocytosis possibly by providing membrane bridges. By quantitatively analyzing membrane contact formation using a novel assay based on quartz crystal microbalance recordings, we show that monomeric AnxA2 can bridge membrane surfaces Ca(2+) dependently. However, this activity depends on an oxidative crosslink involving a cysteine residue in the N-terminal domain and thus formation of disulfide-linked dimers. Alkylated AnxA2 in which this cysteine residue has been modified and AnxA2 mutants lacking the N-terminal domain are not capable of bridging membrane surfaces. In contrast, a heterotetrameric complex comprising two membrane binding AnxA2 subunits linked by a S100A10 dimer can provide membrane contacts irrespective of oxidation status. Thus, monomeric AnxA2 only contains one lipid binding site and AnxA2-mediated linking of membrane surfaces under non-oxidative intracellular conditions most likely requires AnxA2-S100 complex formation. Nature Publishing Group UK 2018-10-02 /pmc/articles/PMC6168566/ /pubmed/30279443 http://dx.doi.org/10.1038/s41598-018-33044-3 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Grill, David Matos, Anna L. L. de Vries, Wilke C. Kudruk, Sergej Heflik, Milena Dörner, Wolfgang Mootz, Henning D. Jan Ravoo, Bart Galla, Hans-Joachim Gerke, Volker Bridging of membrane surfaces by annexin A2 |
title | Bridging of membrane surfaces by annexin A2 |
title_full | Bridging of membrane surfaces by annexin A2 |
title_fullStr | Bridging of membrane surfaces by annexin A2 |
title_full_unstemmed | Bridging of membrane surfaces by annexin A2 |
title_short | Bridging of membrane surfaces by annexin A2 |
title_sort | bridging of membrane surfaces by annexin a2 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168566/ https://www.ncbi.nlm.nih.gov/pubmed/30279443 http://dx.doi.org/10.1038/s41598-018-33044-3 |
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