Nanoscale protein architecture of the kidney glomerular basement membrane

Hani Suleiman, Lei Zhang, Robyn Roth, John E. Heuser, Jeffrey H. Miner, Andrey S. Shaw, Adish Dani

Research output: Contribution to journalArticle

88 Scopus citations

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.

Original languageEnglish
Article numbere01149
JournaleLife
Volume2013
Issue number2
DOIs
StatePublished - Oct 8 2013

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