title: Fscn1 is required for the trafficking of TGF-β family type I receptors during endoderm formation.
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.
authors.affiliation: State Key Laboratory of Membrane Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zhaoting
authors.initials: Z
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Membrane Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Guozhu
authors.initials: G
authors.lastname: Ning
authors.affiliation: State Key Laboratory of Membrane Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Ranran
authors.initials: R
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Membrane Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Anming
authors.initials: A
authors.lastname: Meng
authors.affiliation: State Key Laboratory of Membrane Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.|Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D022163:Clathrin-Coated Vesicles / Q000378:metabolism; D004707:Endoderm / Q000196:embryology* / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D055786:Gene Knockout Techniques; D008297:Male; D008840:Microfilament Proteins / Q000502:physiology*; D023421:Models, Animal; D055457:Nodal Protein / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D015027:Zebrafish / Q000502:physiology; D029961:Zebrafish Proteins / Q000502:physiology*
chemical_list: D008840:Microfilament Proteins; D055457:Nodal Protein; D018125:Receptors, Transforming Growth Factor beta; D029961:Zebrafish Proteins; C000599017:fscn1a protein, zebrafish; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I