dcas supports cell polarization and cell-cell adhesion complexes in developmentdca支持细胞极化,和粘附复合物在发展.pdfVIP

Dcas Supports Cell Polarization and Cell-Cell Adhesion Complexes in Development 1,2 1 1 1 Nadezhda Tikhmyanova , Alexei V. Tulin , Fabrice Roegiers *, Erica A. Golemis * 1 Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America, 2 Department of Biochemistry, Drexel University Medical School, Philadelphia, Pennsylvania, United States of America Abstract Mammalian Cas proteins regulate cell migration, division and survival, and are often deregulated in cancer. However, the presence of four paralogous Cas family members in mammals (BCAR1/p130Cas, EFS/Sin1, NEDD9/HEF1/Cas-L, and CASS4/ HEPL) has limited their analysis in development. We deleted the single Drosophila Cas gene, Dcas, to probe the developmental function of Dcas. Loss of Dcas had limited effect on embryonal development. However, we found that Dcas is an important modulator of the severity of the developmental phenotypes of mutations affecting integrins (If and mew) and their downstream effectors Fak56D or Src42A. Strikingly, embryonic lethal Fak56D-Dcas double mutant embryos had extensive cell polarity defects, including mislocalization and reduced expression of E-cadherin. Further genetic analysis established that loss of Dcas modified the embryonal lethal phenotypes of embryos with mutations in E-cadherin (Shg) or its signaling partners p120- and b-catenin (Arm). These results support an important role for Cas proteins in cell-cell adhesion signaling in development. Citation: Tikhmyanova N, Tulin AV, Roegiers F, Golemis EA (2010) Dcas Supports Cell Polarization and Cell-Cell Adhesion Complexes in Development. PLoS ONE 5(8): e12369. doi:10.1371/journal.pone.0012369 Editor: Madhuri Ka