Src kinases relax adherens junctions between the neighbors of apoptotic cells to permit apical extrusion
Jessica L. Teo, Vanesa M. Tomatis, Luke Coburn, Anne K. Lagendijk, Irin-Maya Schouwenaar, Srikanth Budnar, Thomas E. Hall, Suzie Verma, Robert W. McLachlan, Benjamin M. Hogan, Robert G. Parton, Alpha S. Yap, Guillermo A. Gómez
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. Inhibiting SFK signaling blocks both the expulsion of apoptotic cells and the rosette formation among their neighbor cells. This reveals the complex pattern of spatially distinct contraction and relaxation that must be established in the neighboring epithelium for apoptotic cells to be extruded.