Mechanotransduction activates RhoA in the neighbors of apoptotic epithelial cells to apical extrusion
Kinga Duszyc, Guillermo A Gomez, Anne K Lagendijk, Mei-Kwan Yau, Bageshri Naimish Nanavati, Briony L Gliddon, Thomas E Hall, Suzie Verma, Benjamin M Hogan, Stuart M Pitson, David P Fairlie, Robert G Parton, Alpha S Yap
CURRENT BIOLOGY | CELL PRESS | Published : 2021
Epithelia 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 ..View full abstract
Awarded by National Health and Medical Council of Australia
Awarded by Australian Research Council
We thank our colleagues in the lab for their always-generous gifts of ideas and support and more distant colleagues for their gifts of reagents. This work was supported by project grants and fellowships from the National Health and Medical Council of Australia to A.S.Y. (1123816, 1164462, and 1136592), S.M.P. (1156693), D.P.F. (1117017), B.M.H. (1155221), and R.G.P. (1140064 and 1150083) and the Australian Research Council to A.S.Y. (DP19010287), D.P.F. (DP180103244 and CE140100011), and R.G.P. (Centre of Excellence in Convergent Bio-Nano Science and Technology CE140100036). Optical microscopy was performed at the ACRF/IMB Cancer Biology Imaging Facility, established with the generous support of the Australian Cancer Research Foundation.