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A basement membrane discovery pipeline uncovers network complexity, new regulators, and human disease associations

Authors :
Nikki-Maria Koudis
Damian Smedley
Mychel Rpt Morais
Jamie M Ellingford
Antony Adamson
David R. Sherwood
Maryline Fresquet
Anna S. Li
Sandhya Srinivasan
Eric Hastie
Ranjay Jayadev
Richard W. Naylor
Rachel Lennon
Emily Williams
Raymond T. O'Keefe
Jack F. Ingham
Helen M. Stuart
Craig Lawless
Huw B. Thomas
Qiuyi Chi
Siddharth Banka
Publication Year :
2021
Publisher :
Cold Spring Harbor Laboratory, 2021.

Abstract

SummaryBasement membranes (BMs) are ubiquitous extracellular matrices whose composition remains elusive, limiting our understanding of BM regulation and function. By developing a bioinformatic and in vivo discovery pipeline, we define a network of 222 human proteins localized to BMs. Network analysis and screening in C. elegans and zebrafish identified new BM regulators, including ADAMTS, ROBO, and TGFβ. More than 100 BM-network genes associate with human phenotypes and by screening 63,039 genomes from families with rare disorders, we discovered loss-of-function variants in LAMA5, MPZL2, and MATN2, and show they regulate BM composition and function. This cross-disciplinary study establishes the immense complexity and role of BMs in human health.

Details

Database :
OpenAIRE
Accession number :
edsair.doi...........5abdb5d7cef4df1add0326719cc4136c
Full Text :
https://doi.org/10.1101/2021.10.25.465762