P115 RhoGEF and microtubules decide the direction apoptotic cells extrude from an epithelium.
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.
Slattum
Gloria
G
Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
McGee
Karen M
KM
Rosenblatt
Jody
J
D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D016764:Cell Polarity; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D024462:Myosin Type II / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D064067:Rho Guanine Nucleotide Exchange Factors; D050257:Tubulin Modulators / Q000494:pharmacology; D015027:Zebrafish / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism
C576600:ARHGEF1 protein, human; D000199:Actins; D015415:Biomarkers; D020662:Guanine Nucleotide Exchange Factors; D034741:RNA, Small Interfering; D064067:Rho Guanine Nucleotide Exchange Factors; D050257:Tubulin Modulators; D024462:Myosin Type II; D017239:Paclitaxel; D015739:Nocodazole