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Published online
doi:10.1083/jcb.200903079
The Journal of Cell Biology, Vol. 186, No. 5, 693-702
The Rockefeller University Press, 0021-9525 $30.00
© Slattum et al.
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P115 RhoGEF and microtubules decide the direction apoptotic cells extrude from an epithelium



Gloria Slattum1, Karen M. McGee1,2, and Jody Rosenblatt1

1 Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112
2 Institute of Ophthalmology, London EC1V 9EL, England, UK

Correspondence to Jody Rosenblatt: jody.rosenblatt{at}hci.utah.edu

To preserve epithelial barrier function, dying cells are squeezed out of an epithelium by "apoptotic cell extrusion." Specifically, a cell destined for apoptosis signals its live neighboring epithelial cells to form and contract a ring of actin and myosin II that squeezes the dying cell out of the epithelial sheet. Although most apoptotic cells extrude apically, we find that some exit basally. Localization of actin and myosin IIA contraction dictates the extrusion direction: basal extrusion requires circumferential contraction of neighboring cells at their apices, whereas apical extrusion also requires downward contraction along the basolateral surfaces. To activate actin/myosin basolaterally, microtubules in neighboring cells reorient and target p115 RhoGEF to this site. Preventing microtubule reorientation restricts contraction to the apex, driving extrusion basally. Extrusion polarity has important implications for tumors where apoptosis is blocked but extrusion is not, as basal extrusion could enable these cells to initiate metastasis.

Abbreviations used in this paper: CCD, charge-coupled device; DIC, differential interference contrast; DMEM, Dulbecco's minimum essential medium; LARG, leukemia-associated RhoGEF; RGS, regulator of G protein signaling.

© 2009 Slattum et al.
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