Cargando…
Organisation of extracellular matrix proteins laminin and agrin in pericapillary basal laminae in mouse brain
Evidence suggests that extracellular matrix molecules of perivascular basal laminae help orchestrate the molecular assemblies at the gliovascular interface. Specifically, laminin and agrin are thought to tether the dystrophin-associated protein (DAP) complex to the astrocytic basal lamina. This comp...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046580/ https://www.ncbi.nlm.nih.gov/pubmed/32072250 http://dx.doi.org/10.1007/s00429-020-02036-3 |
_version_ | 1783501976635441152 |
---|---|
author | Hoddevik, Eystein Hellstrøm Rao, Shreyas Balachandra Zahl, Soulmaz Boldt, Henning Bünsow Ottersen, Ole Petter Amiry-Moghaddam, Mahmood |
author_facet | Hoddevik, Eystein Hellstrøm Rao, Shreyas Balachandra Zahl, Soulmaz Boldt, Henning Bünsow Ottersen, Ole Petter Amiry-Moghaddam, Mahmood |
author_sort | Hoddevik, Eystein Hellstrøm |
collection | PubMed |
description | Evidence suggests that extracellular matrix molecules of perivascular basal laminae help orchestrate the molecular assemblies at the gliovascular interface. Specifically, laminin and agrin are thought to tether the dystrophin-associated protein (DAP) complex to the astrocytic basal lamina. This complex includes α-syntrophin (α-Syn), which is believed to anchor aquaporin-4 (AQP4) to astrocytic endfoot membrane domains. We have previously shown that the size of the perivascular AQP4 pool differs considerably between brain regions in an α-Syn-dependent manner. Also, both AQP4 and α-Syn occur at higher densities in endfoot membrane domains facing pericytes than in endfoot membrane domains facing endothelial cells. The heterogeneous distribution of AQP4 at the regional and capillary level has been attributed to a direct interaction between AQP4 and α-Syn. This would be challenged (1) if the microdistributions of laminin and agrin fail to align with those of DAP and AQP4 and (2) if targeted deletion of α-Syn leads to a loss of laminin and/or agrin. Here, we provide the first detailed and quantitative analysis of laminin and agrin in brain basal laminae of mice. We show that the microdistributions of these molecules vary in a fashion that is well aligned with the previously reported microdistribution of AQP4. We also demonstrate that the expression patterns of laminin and agrin are insensitive to targeted deletion of α-Syn, suggesting that α-Syn deletion affects AQP4 directly and not indirectly via laminin or agrin. These data fill remaining voids in the current model of how key molecules are assembled and tethered at the gliovascular interface. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00429-020-02036-3) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-7046580 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-70465802020-03-13 Organisation of extracellular matrix proteins laminin and agrin in pericapillary basal laminae in mouse brain Hoddevik, Eystein Hellstrøm Rao, Shreyas Balachandra Zahl, Soulmaz Boldt, Henning Bünsow Ottersen, Ole Petter Amiry-Moghaddam, Mahmood Brain Struct Funct Original Article Evidence suggests that extracellular matrix molecules of perivascular basal laminae help orchestrate the molecular assemblies at the gliovascular interface. Specifically, laminin and agrin are thought to tether the dystrophin-associated protein (DAP) complex to the astrocytic basal lamina. This complex includes α-syntrophin (α-Syn), which is believed to anchor aquaporin-4 (AQP4) to astrocytic endfoot membrane domains. We have previously shown that the size of the perivascular AQP4 pool differs considerably between brain regions in an α-Syn-dependent manner. Also, both AQP4 and α-Syn occur at higher densities in endfoot membrane domains facing pericytes than in endfoot membrane domains facing endothelial cells. The heterogeneous distribution of AQP4 at the regional and capillary level has been attributed to a direct interaction between AQP4 and α-Syn. This would be challenged (1) if the microdistributions of laminin and agrin fail to align with those of DAP and AQP4 and (2) if targeted deletion of α-Syn leads to a loss of laminin and/or agrin. Here, we provide the first detailed and quantitative analysis of laminin and agrin in brain basal laminae of mice. We show that the microdistributions of these molecules vary in a fashion that is well aligned with the previously reported microdistribution of AQP4. We also demonstrate that the expression patterns of laminin and agrin are insensitive to targeted deletion of α-Syn, suggesting that α-Syn deletion affects AQP4 directly and not indirectly via laminin or agrin. These data fill remaining voids in the current model of how key molecules are assembled and tethered at the gliovascular interface. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00429-020-02036-3) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2020-02-18 2020 /pmc/articles/PMC7046580/ /pubmed/32072250 http://dx.doi.org/10.1007/s00429-020-02036-3 Text en © The Author(s) 2020 Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Original Article Hoddevik, Eystein Hellstrøm Rao, Shreyas Balachandra Zahl, Soulmaz Boldt, Henning Bünsow Ottersen, Ole Petter Amiry-Moghaddam, Mahmood Organisation of extracellular matrix proteins laminin and agrin in pericapillary basal laminae in mouse brain |
title | Organisation of extracellular matrix proteins laminin and agrin in pericapillary basal laminae in mouse brain |
title_full | Organisation of extracellular matrix proteins laminin and agrin in pericapillary basal laminae in mouse brain |
title_fullStr | Organisation of extracellular matrix proteins laminin and agrin in pericapillary basal laminae in mouse brain |
title_full_unstemmed | Organisation of extracellular matrix proteins laminin and agrin in pericapillary basal laminae in mouse brain |
title_short | Organisation of extracellular matrix proteins laminin and agrin in pericapillary basal laminae in mouse brain |
title_sort | organisation of extracellular matrix proteins laminin and agrin in pericapillary basal laminae in mouse brain |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046580/ https://www.ncbi.nlm.nih.gov/pubmed/32072250 http://dx.doi.org/10.1007/s00429-020-02036-3 |
work_keys_str_mv | AT hoddevikeysteinhellstrøm organisationofextracellularmatrixproteinslamininandagrininpericapillarybasallaminaeinmousebrain AT raoshreyasbalachandra organisationofextracellularmatrixproteinslamininandagrininpericapillarybasallaminaeinmousebrain AT zahlsoulmaz organisationofextracellularmatrixproteinslamininandagrininpericapillarybasallaminaeinmousebrain AT boldthenningbunsow organisationofextracellularmatrixproteinslamininandagrininpericapillarybasallaminaeinmousebrain AT ottersenolepetter organisationofextracellularmatrixproteinslamininandagrininpericapillarybasallaminaeinmousebrain AT amirymoghaddammahmood organisationofextracellularmatrixproteinslamininandagrininpericapillarybasallaminaeinmousebrain |