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Basement membrane ligands initiate distinct signalling networks to direct cell shape

Randles, Michael
; 
Lausecker, Franziska
; 
Humphries, Jonathan D.
; 
Byron, Adam
; 
Clark, Simon J.
; 
Miner, Jeffrey H.
; 
Zent, Roy
; 
Humphries, Martin J.
; 
Lennon, Rachel
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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 Chester
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Publication Date
2020-03-06
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Chester Medical School
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Abstract
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.2020.02.005
Publisher
Elsevier
Journal
Matrix Biology
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URI
http://hdl.handle.net/10034/627064
DOI
10.1016/j.matbio.2020.02.005
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Article
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ISSN
0945-053X
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https://www.sciencedirect.com/science/article/pii/S0945053X2030024X
https://pubmed.ncbi.nlm.nih.gov/32147508/