Nanoscale protein architecture of the kidney glomerular basement membrane
In multicellular organisms, proteins of the extracellular matrix (ECM) play structural and functional roles in essentially all organs, so understanding ECM protein organization in health and disease remains an important goal. Here, we used sub-diffraction resolution stochastic optical reconstruction...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2013-10-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/01149 |
| _version_ | 1811200108548587520 |
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| author | Hani Suleiman Lei Zhang Robyn Roth John E Heuser Jeffrey H Miner Andrey S Shaw Adish Dani |
| author_facet | Hani Suleiman Lei Zhang Robyn Roth John E Heuser Jeffrey H Miner Andrey S Shaw Adish Dani |
| author_sort | Hani Suleiman |
| collection | DOAJ |
| description | In multicellular organisms, proteins of the extracellular matrix (ECM) play structural and functional roles in essentially all organs, so understanding ECM protein organization in health and disease remains an important goal. Here, we used sub-diffraction resolution stochastic optical reconstruction microscopy (STORM) to resolve the in situ molecular organization of proteins within the kidney glomerular basement membrane (GBM), an essential mediator of glomerular ultrafiltration. Using multichannel STORM and STORM-electron microscopy correlation, we constructed a molecular reference frame that revealed a laminar organization of ECM proteins within the GBM. Separate analyses of domains near the N- and C-termini of agrin, laminin, and collagen IV in mouse and human GBM revealed a highly oriented macromolecular organization. Our analysis also revealed disruptions in this GBM architecture in a mouse model of Alport syndrome. These results provide the first nanoscopic glimpse into the organization of a complex ECM. |
| first_indexed | 2024-04-12T01:59:14Z |
| format | Article |
| id | doaj.art-6ae1fcc1256c4d77b1238c1bbafde063 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:59:14Z |
| publishDate | 2013-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-6ae1fcc1256c4d77b1238c1bbafde0632022-12-22T03:52:43ZengeLife Sciences Publications LtdeLife2050-084X2013-10-01210.7554/eLife.01149Nanoscale protein architecture of the kidney glomerular basement membraneHani Suleiman0Lei Zhang1Robyn Roth2John E Heuser3Jeffrey H Miner4Andrey S Shaw5Adish Dani6Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United StatesDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, United StatesDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, United StatesDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, United StatesDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, United States; Renal Division, Department of Medicine, Washington University School of Medicine, St. Louis, United StatesDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States; Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, United StatesDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, United StatesIn multicellular organisms, proteins of the extracellular matrix (ECM) play structural and functional roles in essentially all organs, so understanding ECM protein organization in health and disease remains an important goal. Here, we used sub-diffraction resolution stochastic optical reconstruction microscopy (STORM) to resolve the in situ molecular organization of proteins within the kidney glomerular basement membrane (GBM), an essential mediator of glomerular ultrafiltration. Using multichannel STORM and STORM-electron microscopy correlation, we constructed a molecular reference frame that revealed a laminar organization of ECM proteins within the GBM. Separate analyses of domains near the N- and C-termini of agrin, laminin, and collagen IV in mouse and human GBM revealed a highly oriented macromolecular organization. Our analysis also revealed disruptions in this GBM architecture in a mouse model of Alport syndrome. These results provide the first nanoscopic glimpse into the organization of a complex ECM.https://elifesciences.org/articles/01149super-resolution microscopyextracellular matrixkidneybasement membrane |
| spellingShingle | Hani Suleiman Lei Zhang Robyn Roth John E Heuser Jeffrey H Miner Andrey S Shaw Adish Dani Nanoscale protein architecture of the kidney glomerular basement membrane eLife super-resolution microscopy extracellular matrix kidney basement membrane |
| title | Nanoscale protein architecture of the kidney glomerular basement membrane |
| title_full | Nanoscale protein architecture of the kidney glomerular basement membrane |
| title_fullStr | Nanoscale protein architecture of the kidney glomerular basement membrane |
| title_full_unstemmed | Nanoscale protein architecture of the kidney glomerular basement membrane |
| title_short | Nanoscale protein architecture of the kidney glomerular basement membrane |
| title_sort | nanoscale protein architecture of the kidney glomerular basement membrane |
| topic | super-resolution microscopy extracellular matrix kidney basement membrane |
| url | https://elifesciences.org/articles/01149 |
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