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Fscn1 is required for the trafficking of TGF-β family type I receptors during endoderm formation

Zhaoting Liu, Guozhu Ning, Ranran Xu, Yu Cao, Anming Meng () and Qiang Wang ()
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Zhaoting Liu: State Key Laboratory of Membrane Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Zoology, Chinese Academy of Sciences
Guozhu Ning: State Key Laboratory of Membrane Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Zoology, Chinese Academy of Sciences
Ranran Xu: State Key Laboratory of Membrane Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Zoology, Chinese Academy of Sciences
Yu Cao: State Key Laboratory of Membrane Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Zoology, Chinese Academy of Sciences
Anming Meng: Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University
Qiang Wang: State Key Laboratory of Membrane Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Zoology, Chinese Academy of Sciences

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: Abstract Microtubules function in TGF-β signalling by facilitating the cytoplasmic trafficking of internalized receptors and the nucleocytoplasmic shuttling of Smads. However, nothing is known about whether actin filaments are required for these processes. Here we report that zebrafish actin-bundling protein fscn1a is highly expressed in mesendodermal precursors and its expression is directly regulated by the TGF-β superfamily member Nodal. Knockdown or knockout of fscn1a leads to a reduction of Nodal signal transduction and endoderm formation in zebrafish embryos. Fscn1 specifically interacts with TGF-β family type I receptors, and its depletion disrupts the association between receptors and actin filaments and sequesters the internalized receptors into clathrin-coated vesicles. Therefore, Fscn1 acts as a molecular linker between TGF-β family type I receptors and the actin filaments to promote the trafficking of internalized receptors from clathrin-coated vesicles to early endosomes during zebrafish endoderm formation.

Date: 2016
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DOI: 10.1038/ncomms12603

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