title: Nanoscale protein architecture of the kidney glomerular basement membrane.
abstract: 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. DOI:http://dx.doi.org/10.7554/eLife.01149.001.
authors.affiliation: Department of Pathology and Immunology , Washington University School of Medicine , St. Louis , United States.
authors.forename: Hani
authors.initials: H
authors.lastname: Suleiman
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Robyn
authors.initials: R
authors.lastname: Roth
authors.forename: John E
authors.initials: JE
authors.lastname: Heuser
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Miner
authors.forename: Andrey S
authors.initials: AS
authors.lastname: Shaw
authors.forename: Adish
authors.initials: A
authors.lastname: Dani
mesh_terms: D018171:Agrin / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D024141:Collagen Type IV / Q000378:metabolism / Q000648:ultrastructure; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism / Q000648:ultrastructure*; D050533:Glomerular Basement Membrane / Q000378:metabolism / Q000648:ultrastructure*; D005919:Glomerular Filtration Rate; D006801:Humans; D016023:Integrins / Q000378:metabolism / Q000648:ultrastructure; D007797:Laminin / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission / Q000295:instrumentation; D009394:Nephritis, Hereditary / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D020033:Protein Isoforms / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D018171:Agrin; D024141:Collagen Type IV; D016023:Integrins; D007797:Laminin; D020033:Protein Isoforms
keywords: Human; Mouse; basement membrane; extracellular matrix; kidney; super-resolution microscopy