Dcas supports cell polarization and cell-cell adhesion complexes in development.
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 beta-catenin (Arm). These results support an important role for Cas proteins in cell-cell adhesion signaling in development.
Tikhmyanova
Nadezhda
N
Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America.
Tulin
Alexei V
AV
Roegiers
Fabrice
F
Golemis
Erica A
EA
D000483:Alleles; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D016764:Cell Polarity; D003599:Cytoskeleton / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D017353:Gene Deletion; D016023:Integrins / Q000378:metabolism; D007365:Intercellular Junctions / Q000378:metabolism; D008297:Male; D008648:Mesoderm / Q000166:cytology; D009154:Mutation; D010641:Phenotype; D021381:Protein Transport; D013379:Substrate Specificity
D015820:Cadherins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D016023:Integrins; C110593:cas protein, Drosophila
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