PUBLICATION
Endocytic trafficking of rac is required for the spatial restriction of signaling in cell migration
- Authors
- Palamidessi, A., Frittoli, E., Garré, M., Faretta, M., Mione, M., Testa, I., Diaspro, A., Lanzetti, L., Scita, G., and Di Fiore, P.P.
- ID
- ZDB-PUB-080714-13
- Date
- 2008
- Source
- Cell 134(1): 135-147 (Journal)
- Registered Authors
- Mione, Marina
- Keywords
- CELLBIO
- MeSH Terms
-
- Actins/metabolism
- Animals
- Cell Line, Tumor
- Cell Movement*
- Clathrin/metabolism
- Embryo, Mammalian/cytology
- Embryo, Nonmammalian/cytology
- Endocytosis*
- Endosomes/metabolism
- Germ Cells/cytology
- Germ Cells/metabolism
- Hepatocyte Growth Factor/metabolism
- Humans
- Mice
- Proto-Oncogene Proteins c-akt/metabolism*
- Signal Transduction*
- Zebrafish
- rab5 GTP-Binding Proteins/metabolism*
- PubMed
- 18614017 Full text @ Cell
Citation
Palamidessi, A., Frittoli, E., Garré, M., Faretta, M., Mione, M., Testa, I., Diaspro, A., Lanzetti, L., Scita, G., and Di Fiore, P.P. (2008) Endocytic trafficking of rac is required for the spatial restriction of signaling in cell migration. Cell. 134(1):135-147.
Abstract
The small GTPases, Rab5 and Rac, are essential for endocytosis and actin remodeling, respectively. Coordination of these processes is critical to achieve spatial restriction of intracellular signaling, which is essential for a variety of polarized functions. Here, we show that clathrin- and Rab5-mediated endocytosis are required for the activation of Rac induced by motogenic stimuli. Rac activation occurs on early endosomes, where the RacGEF Tiam1 is also recruited. Subsequent recycling of Rac to the plasma membrane ensures localized signaling, leading to the formation of actin-based migratory protrusions. Thus, membrane trafficking of Rac is required for the spatial resolution of Rac-dependent motogenic signals. We further demonstrate that a Rab5-to-Rac circuitry controls the morphology of motile mammalian tumor cells and primordial germinal cells during zebrafish development, suggesting that this circuitry is relevant for the regulation of migratory programs in various cells, in both in vitro settings and whole organisms.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping