Journal
DEVELOPMENTAL CELL
Volume 19, Issue 3, Pages 426-439Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2010.08.007
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Funding
- National Cancer Institute of Canada
- Canadian Cancer Society Research Institute, CCSRI
- National Science and Engineering Research Council of Canada (NSERC)
- Fonds de la Recherche en Sante du Quebec (FRSQ)
- Canadian Institutes of Health Research (CIHR)
- Fonds Quebecois de la Recherche sur la Nature et les Technologies (FQRNT)
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Targeting of activated plasma membrane receptors to endocytic pathways is important in determining the outcome of growth factor signaling. However, the molecular mechanisms are still poorly understood. Here, we show that the synaptotagminrelated membrane protein E-Syt2 is essential for rapid endocytosis of the activated FGF receptor and for functional signal transduction during Xenopus development. E-Syt2 depletion prevents an early phase of activated FGF receptor endocytosis that we show is required for ERK activation and the induction of the mesoderm. E-Syt2 interacts selectively with the activated FGF receptor and with Adaptin-2, and is required upstream of Ras activation and of receptor autophosphorylation for ERK activation and the induction of the mesodermal marker Xbra. The data identify E-Syt2 as an endocytic adaptor for the clathrin-mediated pathway whose function is conserved in human and suggest a broader role for the E-Syt subfamily in growth factor signaling.
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