MATN2 knock-down human immortalized podocytes LC-MS/MS

Basement 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 over 220 human proteins localized to BMs. More than 100 BM-network genes associate with human phenotypes and by screening over 63,000 germline genomic sequences from families with rare disorders, we discovered novel predicted loss-of-function variants in MATN2. Biochemical analyses suggest that MATN2 interacts with many BM proteins, and we found that depletion of MATN2 affected levels of core BM components in human podocyte-derived extracellular matrix.