Mechanotransduction activates RhoA in the neighbors of apoptotic epithelial cells to engage apical extrusion

Simple item page
dc.contributor.authorDuszyc, K.
dc.contributor.authorGomez, G.A.
dc.contributor.authorLagendijk, A.K.
dc.contributor.authorYau, M.K.
dc.contributor.authorNanavati, B.N.
dc.contributor.authorGliddon, B.L.
dc.contributor.authorHall, T.E.
dc.contributor.authorVerma, S.
dc.contributor.authorHogan, B.M.
dc.contributor.authorPitson, S.M.
dc.contributor.authorFairlie, D.P.
dc.contributor.authorParton, R.G.
dc.contributor.authorYap, A.S.
dc.date.issued2021
dc.description.abstractEpithelia must eliminate apoptotic cells to preserve tissue barriers and prevent inflammation.1 Several different mechanisms exist for apoptotic clearance, including efferocytosis2,3 and apical extrusion.4,5 We found that extrusion was the first-line response to apoptosis in cultured monolayers and in zebrafish epidermis. During extrusion, the apoptotic cell elicited active lamellipodial protrusions and assembly of a contractile extrusion ring in its neighbors. Depleting E-cadherin compromised both the contractile ring and extrusion, implying that a cadherin-dependent pathway allows apoptotic cells to engage their neighbors for extrusion. We identify RhoA as the cadherin-dependent signal in the neighbor cells and show that it is activated in response to contractile tension from the apoptotic cell. This mechanical stimulus is conveyed by a myosin-VI-dependent mechanotransduction pathway that is necessary both for extrusion and to preserve the epithelial barrier when apoptosis was stimulated. Earlier studies suggested that release of sphingosine-1-phosphate (S1P) from apoptotic cells might define where RhoA was activated. However, we found that, although S1P is necessary for extrusion, its contribution does not require a localized source of S1P in the epithelium. We therefore propose a unified view of how RhoA is stimulated to engage neighbor cells for apoptotic extrusion. Here, tension-sensitive mechanotransduction is the proximate mechanism that activates RhoA specifically in the immediate neighbors of apoptotic cells, but this also must be primed by S1P in the tissue environment. Together, these elements provide a coincidence detection system that confers robustness on the extrusion response.
dc.description.statementofresponsibilityKinga Duszyc, Guillermo A. Gomez, Anne K. Lagendijk, Mei-Kwan Yau, Bageshri Naimish Nanavati, Briony L. Gliddon ... et al.
dc.identifier.citationCurrent Biology, 2021; 31(6):1326-1336
dc.identifier.doi10.1016/j.cub.2021.01.003
dc.identifier.issn0960-9822
dc.identifier.issn1879-0445
dc.identifier.orcidPitson, S.M. [0000-0002-9527-2740]
dc.identifier.urihttp://hdl.handle.net/2440/131641
dc.language.isoen
dc.publisherElsevier
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1123816
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1164462
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1136592
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1155221
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1156693
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1117017
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1150083
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1140064
dc.relation.granthttp://purl.org/au-research/grants/arc/CE140100036
dc.relation.granthttp://purl.org/au-research/grants/arc/CE140100011
dc.relation.granthttp://purl.org/au-research/grants/arc/DP180103244
dc.relation.granthttp://purl.org/au-research/grants/arc/DP19010287
dc.rights© 2021 Elsevier Inc.
dc.source.urihttps://doi.org/10.1016/j.cub.2021.01.003
dc.subjectRhoA
dc.subjectapical extrusion
dc.subjectapoptotic elimination
dc.subjectepithelial apoptosis
dc.subjectmechanotransduction
dc.titleMechanotransduction activates RhoA in the neighbors of apoptotic epithelial cells to engage apical extrusion
dc.typeJournal article
pubs.publication-statusPublished

Files

Collections

Environment Institute publications