DASPP/BOA PROTEINS · Functional Analysis of dASPP/Boa, novel regulators of dCsk in epithelial growth and morphogenesis
FP7 — People (Marie Curie Actions)
- Duration
- 2009-10-01 → 2011-09-30
- EU contribution
- €171,301
- Participants
- 1
- Scheme
- MC-IEF
Lines connect the coordinator with its partners.
Results in brief
Functional Analysis of dASPP/Boa, novel regulators of dCsk in epithelial growth and morphogenesis
Final Publishable Summary Report Please see attached document for porject objectives and work performed. A description of the main results achieved so far We previously identified boa/dASPP complex as novel AJ component required for the proper localisation of DE-cadherin. I set out to elucidate the mechanism by which Boa affects AJ stability and found that Boa binds to Sec15, an exocyst component regulating polarised vesicle trafficking. Similar to Sec15 mutants, Boa mutants show an accumulation of Rab11-containing recycling endosomes, suggesting defects in the vesicle trafficking pathway. Boa also genetically interacts with Sec15. Electron microscopy data shows that Boa mutants seem to have a defect in the organization of the vesicle sorting pathway. In order to study the dynamics of the AJs and vesicles in living animal, we have now set up live-imaging and FRAP analysis in developing mosaic pupal retinas which allows us to perform clonal analysis live. Expected final results Once I finish performing the in vivo live-imaging/ FRAP experiments and analysing the data, I will have quantitative data to show the effect of Boa in AJs and vesicle dynamics. The results from the 3D TEM experiment will provide further information on the defect of vesicle trafficking pathway in Boa mutants. I will then have a complete picture of the functions of Boa/sec15 complex in AJs maintenance. My findings show that Boa, together with Sec15 modulates polarised vesicle trafficking and thus AJs stability during epithelial morphogenesis.
Data: CORDIS, © European Union
Project objective
Src-family kinases play major roles in promoting adherens junctions remodelling in development and metastasis. Their activities are negatively regulated by C-terminal Src kinase (Csk). The host lab it has recently shown that Drosophila Ankyrin-repeat, SH3-domain and Proline-rich-region containing (dASPP), together with Boa the homology of mammalian Ras association domain family 8, regulates the function of dCsk in maintaining adherens junctions polarity and integrity in Drosophila (Langton et al., 2007 and unpublished data). However, the molecular nature of this interaction and the exact functions of dASPP and Boa on developing epithelia are still unknown. In this research project, we propose to address the molecular mechanism by which dASPP and Boa regulates dCsk activity and their function in epithelial growth and morphogenesis during development, as well as identify new regulators of Src signalling in epithelial cells.
Original text from CORDIS.
Participants
- CANCER RESEARCH UK LBG · LONDONCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union