PUBLICATION

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

Authors
Liu, Z., Ning, G., Xu, R., Cao, Y., Meng, A., Wang, Q.
ID
ZDB-PUB-160823-6
Date
2016
Source
Nature communications   7: 12603 (Journal)
Registered Authors
Meng, Anming, Wang, Qiang
Keywords
Actin, Cell lineage, Endocytosis, Morphogen signalling
MeSH Terms
  • Actin Cytoskeleton/metabolism
  • Animals
  • Clathrin-Coated Vesicles/metabolism
  • Endoderm/embryology*
  • Endoderm/metabolism
  • Endosomes/metabolism
  • Female
  • Gene Knockdown Techniques
  • Gene Knockout Techniques
  • Male
  • Microfilament Proteins/physiology*
  • Models, Animal
  • Nodal Protein/metabolism*
  • Protein Serine-Threonine Kinases/metabolism*
  • Protein Transport/physiology
  • Receptors, Transforming Growth Factor beta/metabolism*
  • Signal Transduction/physiology*
  • Zebrafish/physiology
  • Zebrafish Proteins/physiology*
PubMed
27545838 Full text @ Nat. Commun.
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.
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