PUBLICATION

Identification of myosin II as a cripto binding protein and regulator of cripto function in stem cells and tissue regeneration

Authors
Hoover, M., Runa, F., Booker, E., Diedrich, J.K., Duell, E., Williams, B., Arellano-Garcia, C., Uhlendorf, T., La Kim, S., Fischer, W., Moresco, J., Gray, P.C., Kelber, J.A.
ID
ZDB-PUB-181224-22
Date
2018
Source
Biochemical and Biophysical Research Communications   509(1): 69-75 (Journal)
Registered Authors
Keywords
Actomyosin signaling, Cripto, Proteomics, Stem cells, Tissue regeneration, Zebrafish
MeSH Terms
  • Animal Fins/physiology*
  • Animals
  • Cell Line
  • Cell Proliferation
  • Homeodomain Proteins/metabolism*
  • Humans
  • Mesenchymal Stem Cells/cytology
  • Mesenchymal Stem Cells/metabolism
  • Myosin Type II/metabolism*
  • Protein Interaction Maps*
  • Regeneration*
  • Stem Cells/cytology*
  • Stem Cells/metabolism
  • Transcription Factors/metabolism*
  • Wound Healing
  • Zebrafish/physiology*
  • Zebrafish Proteins/metabolism*
PubMed
30579599 Full text @ Biochem. Biophys. Res. Commun.
Abstract
Cripto regulates stem cell function in normal and disease contexts via TGFbeta/activin/nodal, PI3K/Akt, MAPK and Wnt signaling. Still, the molecular mechanisms that govern these pleiotropic functions of Cripto remain poorly understood. We performed an unbiased screen for novel Cripto binding proteins using proteomics-based methods, and identified novel proteins including members of myosin II complexes, the actin cytoskeleton, the cellular stress response, and extracellular exosomes. We report that myosin II, and upstream ROCK1/2 activities are required for localization of Cripto to cytoplasm/membrane domains and its subsequent release into the conditioned media fraction of cultured cells. Functionally, we demonstrate that soluble Cripto (one-eyed pinhead in zebrafish) promotes proliferation in mesenchymal stem cells (MSCs) and stem cell-mediated wound healing in the zebrafish caudal fin model of regeneration. Notably, we demonstrate that both Cripto and myosin II inhibitors attenuated regeneration to a similar degree and in a non-additive manner. Taken together, our data present a novel role for myosin II function in regulating subcellular Cripto localization and function in stem cells and an important regulatory mechanism of tissue regeneration. Importantly, these insights may further the development of context-dependent Cripto agonists and antagonists for therapeutic benefit.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping