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dc.contributor.authorRandles, Michael
dc.contributor.authorLausecker, Franziska
dc.contributor.authorHumphries, Jonathan D.
dc.contributor.authorByron, Adam
dc.contributor.authorClark, Simon J.
dc.contributor.authorMiner, Jeffrey H.
dc.contributor.authorZent, Roy
dc.contributor.authorHumphries, Martin J.
dc.contributor.authorLennon, Rachel
dc.date.accessioned2022-08-02T12:47:56Z
dc.date.available2022-08-02T12:47:56Z
dc.date.issued2020-03-06
dc.identifierhttps://chesterrep.openrepository.com/bitstream/handle/10034/627064/1-s2.0-S0945053X2030024X-main.pdf?sequence=1
dc.identifier.citationRandles, 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.2020.02.005en_US
dc.identifier.issn0945-053X
dc.identifier.doi10.1016/j.matbio.2020.02.005
dc.identifier.urihttp://hdl.handle.net/10034/627064
dc.description.abstractCells 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.en_US
dc.publisherElsevieren_US
dc.relation.urlhttps://www.sciencedirect.com/science/article/pii/S0945053X2030024Xen_US
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/32147508/
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.subjectbasement membraneen_US
dc.subjectType IV collagenen_US
dc.subjectLamininen_US
dc.subjectAdhesomeen_US
dc.subjectCell shapeen_US
dc.subjectRac1en_US
dc.subjectPKCen_US
dc.titleBasement membrane ligands initiate distinct signalling networks to direct cell shapeen_US
dc.typeArticleen_US
dc.contributor.departmentThe 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 Chesteren_US
dc.identifier.journalMatrix Biologyen_US
or.grant.openaccessYesen_US
rioxxterms.funderWellcome Trust Senior Fellowship award (202860/Z/16/Z)en_US
rioxxterms.identifier.projectWellcome Trust Senior Fellowship award (202860/Z/16/Z)en_US
rioxxterms.versionVoRen_US
rioxxterms.versionofrecord10.1016/j.matbio.2020.02.005en_US
dcterms.dateAccepted2020-02-29
rioxxterms.publicationdate2020-03-06
dc.date.deposited2022-08-02en_US
dc.indentifier.issn0945-053Xen_US


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