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XB-ART-42034
Dev Cell September 14, 2010; 19 (3): 426-39.

Extended-synaptotagmin-2 mediates FGF receptor endocytosis and ERK activation in vivo.

Jean S , Mikryukov A , Tremblay MG , Baril J , Guillou F , Bellenfant S , Moss T .


Abstract
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 synaptotagmin-related 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.

PubMed ID: 20833364
Article link: Dev Cell
Grant support: [+]
Genes referenced: acss2.1 acss2.2 akt1 cltc ctrl esyt2 fgf2 fgf8 fgfr1 mapk1 myc pik3ca syt1 syt2 tbxt tubb2b
Morpholinos: esyt2 MO1 esyt2 MO2 esyt2 MO3 esyt2 MO4 esyt2 MO5


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