ReviewProteomic definitions of basement membrane composition in health and disease

- Basement membrane protein and mRNA abundance correlate poorly, due to long protein half-lives and regulation by protoelytic degradation.
- Basement membranes are frequently embedded within complex structures, are highly crosslinked and insoluble making biochemical analysis challenging.
- Mass spectrometry-based proteomics enables global, unbiased quantification of matrix proteins, including basement membranes components.
- Exploiting the insolubility of basement membranes, sequential detergent extraction approaches enable excellent coverage of basement membrane proteomes.
- Proteomic analysis of basement membranes has been performed in a wide range of tissues and disease contexts, revealing mechanistic insight in cancer metastasis, lung fibrosis and cardiovascular disease.
- The global analysis of post-translational modification is also possible with techniques such as glycoproteomics and degradomics.

Basement membranes are formed from condensed networks of extracellular matrix (ECM) proteins. These structures underlie all epithelial, mesothelial and endothelial sheets and provide an essential structural scaffold. Candidate-based investigations have established that predominant components of basement membranes are laminins, collagen type IV, nidogens and heparan sulphate proteoglycans. More recently, global proteomic approaches have been applied to investigate ECM and these analyses confirm tissue-specific ECM proteomes with a high degree of complexity. The proteomes consist of structural as well as regulatory ECM proteins such as proteases and growth factors. This review is focused on the proteomic analysis of basement membranes and illustrates how this approach can be used to build our understanding of ECM regulation in health and disease.