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

Malachia Hoover, Farhana Runa, Evan Booker, Jolene K. Diedrich, Erika Duell, Blake Williams, Caroline Arellano-Garcia, Toni Uhlendorf, Sa La Kim, Wolfgang Fischer, James Moresco, Peter C. Gray, Jonathan A. Kelber

Research output: Contribution to journalArticle

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)69-75
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume509
Issue number1
DOIs
StatePublished - Jan 29 2019
Externally publishedYes

Keywords

  • Actomyosin signaling
  • Cripto
  • Proteomics
  • Stem cells
  • Tissue regeneration
  • Zebrafish

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    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. (2019). Identification of myosin II as a cripto binding protein and regulator of cripto function in stem cells and tissue regeneration. Biochemical and Biophysical Research Communications, 509(1), 69-75. https://doi.org/10.1016/j.bbrc.2018.12.059