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*
(all 19)
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.
Genes / Markers
Marker Marker Type Name
dlx2aGENEdistal-less homeobox 2a
efnb2bGENEephrin-B2b
eve1GENEeven-skipped-like1
foxa1GENEforkhead box A1
foxd3GENEforkhead box D3
fscn1aGENEfascin actin-bundling protein 1a
fscn1bGENEfascin actin-bundling protein 1b
gata2aGENEGATA binding protein 2a
gata5GENEGATA binding protein 5
gscGENEgoosecoid
1 - 10 of 22
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Figures
Figure Gallery (16 images) / 2
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
TUchemical treatment: dynasoreShield
TUchemical treatment: dynasoreShield
TUchemical treatment: dynasoreShield
TUchemical treatment: latrunculin AShield
TUchemical treatment: latrunculin AShield
TUchemical treatment: latrunculin AShield
TUchemical treatment: latrunculin AShield
TUchemical treatment: latrunculin AShield
TU + MO1-fscn1astandard conditionsShield
TU + MO1-fscn1astandard conditionsShield
1 - 10 of 58
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ioz100
    		Indel
    tz257
      		Point Mutation
      zdf1
        		Point Mutation
        1 - 3 of 3
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        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        fscn1aMO1-fscn1aMRPHLNO
        fscn1aMO2-fscn1aMRPHLNO
        fscn1aTALEN2-fscn1aTALEN
        tp53MO4-tp53MRPHLNO
        1 - 4 of 4
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        Fish
        Fish
        fscn1aioz100/ioz100
        fscn1aioz100/ioz100 + MO1-fscn1a
        tdgf1tz257/tz257
        TU
        TU + MO1-fscn1a
        1 - 5 of 5
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        Antibodies
        Name Type Antigen Genes Isotypes Host Organism
        Ab1-fscn1monoclonalIgGRabbit
        Ab3-smad2polyclonal
          		Rabbit
          1 - 2 of 2
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          Orthology
          No data available
          Engineered Foreign Genes
          No data available
          Mapping
          No data available
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          Citation
          Liu, Z., Ning, G., Xu, R., Cao, Y., Meng, A., Wang, Q. (2016) Fscn1 is required for the trafficking of TGF-β family type I receptors during endoderm formation. Nature communications. 7:12603.