Basement membrane ligands initiate distinct signalling networks to direct cell shape
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Authors
Randles, MichaelLausecker, Franziska
Humphries, Jonathan D.
Byron, Adam
Clark, Simon J.
Miner, Jeffrey H.
Zent, Roy
Humphries, Martin J.
Lennon, Rachel
Affiliation
The University of Manchester; University of Edinburgh; Eberhard Karls University of Tübingen; Washington University School of Medicine; Vanderbilt University Medical Center; Royal Manchester Children's Hospital; Manchester Academic Health Science Centre; University of ChesterPublication Date
2020-03-06
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Cells have evolved mechanisms to sense the composition of their adhesive microenvironment. Although much is known about general mechanisms employed by adhesion receptors to relay signals between the extracellular environment and the cytoskeleton, the nuances of ligand-specific signalling remain undefined. Here, we investigated how glomerular podocytes, and four other basement membrane-associated cell types, respond morphologically to different basement membrane ligands. We defined the composition of the respective adhesion complexes using mass spectrometry-based proteomics. On type IV collagen, all epithelial cell types adopted a round morphology, with a single lamellipodium and large adhesion complexes rich in actin-binding proteins. On laminin (511 or 521), all cell types attached to a similar degree but were polygonal in shape with small adhesion complexes enriched in endocytic and microtubule-binding proteins. Consistent with their distinctive morphologies, cells on type IV collagen exhibited high Rac1 activity, while those on laminin had elevated PKCa. Perturbation of PKCa was able to interchange morphology consistent with a key role for this pathway in matrix ligand-specific signalling. Therefore, this study defines the switchable basement membrane adhesome and highlights two key signalling pathways within the systems that determine distinct cell morphologies. Proteomic data are available via ProteomeXchange with identifier PXD017913.Citation
Randles, M. J., Lausecker, F., Humphries, J. D., Byron, A., Clark, S. J., Miner, J. H., Zent, R., Humphries, M. J., & Lennon, R. (2020). Basement membrane ligands initiate distinct signalling networks to direct cell shape. Matrix Biology, 90, 61-78. https://doi.org/10.1016/j.matbio.2020.02.005Publisher
ElsevierJournal
Matrix BiologyAdditional Links
https://www.sciencedirect.com/science/article/pii/S0945053X2030024Xhttps://pubmed.ncbi.nlm.nih.gov/32147508/
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ArticleISSN
0945-053Xae974a485f413a2113503eed53cd6c53
10.1016/j.matbio.2020.02.005
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Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0/