Journal article
Src kinases relax adherens junctions between the neighbors of apoptotic cells to permit apical extrusion
JL Teo, VM Tomatis, L Coburn, AK Lagendijk, IM Schouwenaar, S Budnar, TE Hall, S Verma, RW McLachlan, BM Hogan, RG Parton, AS Yap, GA Gomez
Molecular Biology of the Cell | AMER SOC CELL BIOLOGY | Published : 2020
Abstract
Epithelia can eliminate apoptotic cells by apical extrusion. This is a complex morphogenetic event where expulsion of the apoptotic cell is accompanied by rearrangement of its immediate neighbors to form a rosette. A key mechanism for extrusion is constriction of an actomyosin network that neighbor cells form at their interface with the apoptotic cell. Here we report a complementary process of cytoskeletal relaxation that occurs when cortical contractility is down-regulated at the junctions between those neighbor cells themselves. This reflects a mechanosensitive Src family kinase (SFK) signaling pathway that is activated in neighbor cells when the apoptotic cell relaxes shortly after injury..
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Grants
Awarded by Institute for Mind and Body, University of Chicago
Funding Acknowledgements
We thank our lab colleagues for their continuous support and fellowship and our many colleagues who generously provided reagents for this project. This work was supported by project grant funding from the National Health and Medical Research Council (NHMRC) Australia (1067405 and 1123816 to A.Y. and G.A.G.; 1037320 1163462 to A.Y.; 1140064 and 1150083 to RGP and 1099251 to T.E.H. and R.G.P.). A.Y. and R.G.P. are Research Fellows of the NHMRC (1136592 and 1156489, respectively). L.C. was funded under the Higher Education Authority of Ireland's Programme for Research in Third Level Institutions (PRTLI) Cycle 5 Simulation Science and cofunded by the European Regional Development Fund (ERDF). G.A.G. is supported by an Australian Research Council Future Fellowship (FT160100366). R.G.P. is supported by the Australian Research Council (ARC) Centre of Excellence in Convergent Bio-Nano Science and Technology. R.W.M. was a recipient of a Queensland Cancer Council PhD scholarship. Optical microscopy was performed at the ACRF/IMB Cancer Biology Imaging Facility, established with the generous support of the Australian Cancer Research Foundation. G.A.G. and V.M.T. dedicate this manuscript to the memory of Jose L. Daniotti (CIQUIBICCONICET), who taught us how to look to the biology of cells.