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been implicated in the activation of epithelial cell motility (Santy and
Casanova, 2001). PLD is also activated and required during FcgR-mediated
phagocytosis, and it has been suggested that ARF6 could be involved in PLD
activation following FcgR engagement (Kusner et al., 1999; Melendez et al.,
2001). There are also clear indications that PIP
2
accumulates in the forming
pseudopods at the onset of phagocytosis, however it is not known whether
ARF6 regulates this PIP
2
production (Botelho et al., 2000). It is anticipated
that activation of PLD and PIP 5K by ARF6 should have a major impact on
the organization and property of the cell cortex, as PA and PIP
2
are well-
known regulators of membrane tracking and actin cytoskeleton remodel-
ling. By analogy with other small GTP-binding proteins, it is very likely that
ARF6 performs multiple functions at various stages of the recycling pathway
including control of vesicle movement, vesicle docking and fusion with the
plasma membrane. PLD and PIP 5K are certainly not the only players and it
is time to compile a comprehensive list of proteins that interact with GTP-
bound ARF6, and to understand the mechanism of their activation by this
fascinating small G protein.
Acknowledgements
We are grateful to Dr J. Plastino for critical reading of the manuscript. This
work was supported by institutional funding from the CNRS and grants from
the Institut Curie, the PRFMMIP (Programme de Recherche Fondamentale
en Microbiologie et Maladies Infectieuses et Parasitaires) and the Ligue
Nationale contre le Cancer. TD is a recipient of a post-doctoral fellowship
from ARC (Association pour la Recherche contre le Cancer).
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