The dASPP-dRASSF8 complex regulates cell-cell adhesion during Drosophila retinal morphogenesis.
BACKGROUND
Adherens junctions (AJs) provide structure to epithelial tissues by connecting adjacent cells through homophilic E-cadherin interactions and are linked to the actin cytoskeleton via the intermediate binding proteins beta-catenin and alpha-catenin. Rather than being static structures, AJs are extensively remodeled during development, allowing the cell rearrangements required for morphogenesis. Several "noncore" AJ components have been identified, which modulate AJs to promote this plasticity but are not absolutely required for cell-cell adhesion.


RESULTS
We previously identified dASPP as a positive regulator of dCsk (Drosophila C-terminal Src kinase). Here we show that dRASSF8, the Drosophila RASSF8 homolog, binds to dASPP and that this interaction is required for normal dASPP levels. Our genetic and biochemical data suggest that dRASSF8 acts in concert with dASPP to promote dCsk activity. Both proteins specifically localize to AJs and are mutually required for each other's localization. Furthermore, we observed abnormal E-cadherin localization in mutant pupal retinas, correlating with aberrant cellular arrangements. Loss of dCsk or overexpression of Src elicited similar AJ defects.


CONCLUSIONS
Because Src is known to regulate AJs in both Drosophila and mammals, we propose that dASPP and dRASSF8 fine tune cell-cell adhesion during development by directing dCsk and Src activity. We show that the dASPP-dRASSF8 interaction is conserved in humans, suggesting that mammalian ASPP1/2 and RASSF8, which are candidate tumor-suppressor genes, restrict the activity of the Src proto-oncogene.
Langton
Paul F
PF
Apoptosis and Proliferation Control Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Colombani
Julien
J
Chan
Eunice H Y
EH
Wepf
Alexander
A
Gstaiger
Matthias
M
Tapon
Nicolas
N
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D011485:Protein Binding; D000090063:Proto-Oncogene Mas; D012160:Retina / Q000196:embryology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D014921:Wings, Animal
C548148:ASPP protein, Drosophila; D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C548149:RASSF8 protein, Drosophila; D025521:Tumor Suppressor Proteins