期刊
JOURNAL OF CELL BIOLOGY
卷 186, 期 5, 页码 693-702出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200903079
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资金
- Cancer Research UK project [C8836/A3275]
- Biotechnology and Biological Sciences Research [31/C18722]
- National Institutes of Health Innovator Award [DP2 OD002056-01, P30 CA042014]
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 re-orientation 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.
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