Back to Search
Start Over
GTP exchange factor Vav regulates guided cell migration by coupling guidance receptor signalling to local Rac activation.
- Source :
-
Journal of cell science [J Cell Sci] 2013 May 15; Vol. 126 (Pt 10), pp. 2285-93. Date of Electronic Publication: 2013 Mar 22. - Publication Year :
- 2013
-
Abstract
- Guided cell migration is a key mechanism for cell positioning in morphogenesis. The current model suggests that the spatially controlled activation of receptor tyrosine kinases (RTKs) by guidance cues limits Rac activity at the leading edge, which is crucial for establishing and maintaining polarized cell protrusions at the front. However, little is known about the mechanisms by which RTKs control the local activation of Rac. Here, using a multidisciplinary approach, we identify the GTP exchange factor (GEF) Vav as a key regulator of Rac activity downstream of RTKs in a developmentally regulated cell migration event, that of the Drosophila border cells (BCs). We show that elimination of the vav gene impairs BC migration. Live imaging analysis reveals that vav is required for the stabilization and maintenance of protrusions at the front of the BC cluster. In addition, activation of the PDGF/VEGF-related receptor (PVR) by its ligand the PDGF/PVF1 factor brings about activation of Vav protein by direct interaction with the intracellular domain of PVR. Finally, FRET analyses demonstrate that Vav is required in BCs for the asymmetric distribution of Rac activity at the front. Our results unravel an important role for the Vav proteins as signal transducers that couple signalling downstream of RTKs with local Rac activation during morphogenetic movements.
- Subjects :
- Animals
Animals, Genetically Modified
Cell Movement genetics
Cell Surface Extensions genetics
Cells, Cultured
Drosophila melanogaster cytology
Embryo, Nonmammalian cytology
Embryo, Nonmammalian metabolism
Enzyme Repression genetics
Female
Morphogenesis genetics
Proto-Oncogene Proteins c-vav genetics
RNA, Small Interfering genetics
Sequence Deletion genetics
Two-Hybrid System Techniques
Drosophila melanogaster physiology
Proto-Oncogene Proteins c-akt metabolism
Proto-Oncogene Proteins c-vav metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9137
- Volume :
- 126
- Issue :
- Pt 10
- Database :
- MEDLINE
- Journal :
- Journal of cell science
- Publication Type :
- Academic Journal
- Accession number :
- 23525006
- Full Text :
- https://doi.org/10.1242/jcs.124438