Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Epithelial cell extrusion requires the sphingosine-1-phosphate receptor 2 pathway.

To maintain an intact barrier, epithelia eliminate dying cells by extrusion. During extrusion, a cell destined for apoptosis signals its neighboring cells to form and contract a ring of actin and myosin, which squeezes the dying cell out of the epithelium. Here, we demonstrate that the signal produced by dying cells to initiate this process is sphingosine-1-phosphate (S1P). Decreasing S1P synthesis by inhibiting sphingosine kinase activity or by blocking extracellular S1P access to its receptor prevented apoptotic cell extrusion. Extracellular S1P activates extrusion by binding the S1P(2) receptor in the cells neighboring a dying cell, as S1P(2) knockdown in these cells or its loss in a zebrafish mutant disrupted cell extrusion. Because live cells can also be extruded, we predict that this S1P pathway may also be important for driving delamination of stem cells during differentiation or invasion of cancer cells.

Pubmed ID: 21555463


  • Gu Y
  • Forostyan T
  • Sabbadini R
  • Rosenblatt J


The Journal of cell biology

Publication Data

May 16, 2011

Associated Grants

  • Agency: NIH HHS, Id: DP2 OD002056
  • Agency: NIH HHS, Id: DP2 OD002056-01
  • Agency: NIH HHS, Id: DP2 OD002056-01
  • Agency: NCI NIH HHS, Id: P30 CA042014

Mesh Terms

  • Actomyosin
  • Animals
  • Antibodies, Monoclonal
  • Apoptosis
  • Cell Line
  • Dogs
  • Enzyme Inhibitors
  • Epithelial Cells
  • Gene Knockdown Techniques
  • Lysophospholipids
  • Mutation
  • Phosphotransferases (Alcohol Group Acceptor)
  • RNA Interference
  • Receptors, Lysosphingolipid
  • Signal Transduction
  • Sphingosine
  • Zebrafish
  • Zebrafish Proteins