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TGF-beta signaling-mediated morphogenesis: modulation of cell adhesion via cadherin endocytosis

Souichi Ogata1, Junji Morokuma, Tadayoshi Hayata

  • 1Department of Developmental and Cell Biology, Developmental Biology Center, University of California at Irvine, Irvine, California 92697, USA.

Genes & Development
|July 20, 2007
PubMed

Insights

This study reveals a new mechanism of cell movement during vertebrate development. Transforming growth factor-beta (TGF-beta) signaling controls cell adhesion through Fibronectin Leucine-rich Repeat Transmembrane 3 (FLRT3) and Rnd1, impacting morphogenesis.

Area of Science:

  • Developmental Biology
  • Cell Biology
  • Molecular Biology

Background:

  • Morphogenesis relies on complex cell behaviors, with Transforming Growth Factor-beta (TGF-beta) ligands influencing cell fate via Smad signaling.
  • The precise role of TGF-beta in guiding cellular morphogenesis across diverse biological contexts remains incompletely understood.
  • Understanding these mechanisms is crucial for both developmental biology and cancer research.

Purpose of the Study:

  • To investigate a novel TGF-beta signaling-mediated pathway regulating cellular morphogenesis during vertebrate gastrulation.
  • To identify key molecular players involved in TGF-beta-induced cell adhesion changes during embryogenesis.
  • To elucidate the mechanism by which these molecules dynamically control cell adhesion.

Main Methods:

  • Utilized vertebrate gastrulation models to study TGF-beta signaling.
  • Investigated the roles of Fibronectin Leucine-rich Repeat Transmembrane 3 (FLRT3) and Rnd1 in cell adhesion.
  • Analyzed the interaction between FLRT3, Rnd1, and cadherins using dynamin-dependent endocytosis pathways.

Main Results:

  • Discovered that Activin/nodal members of the TGF-beta superfamily induce FLRT3 and Rnd1 expression during gastrulation.
  • Demonstrated that FLRT3 and Rnd1 physically interact and modulate cell adhesion by controlling cell surface cadherin levels.
  • Showed that this modulation occurs via a dynamin-dependent endocytosis pathway, regulating cadherin internalization and redeployment.

Conclusions:

  • A novel TGF-beta-FLRT3-Rnd1 pathway dynamically regulates cell adhesion during vertebrate gastrulation by controlling cadherin trafficking.
  • This mechanism involves the internalization and recycling of cadherins, offering a new model for dynamic cell adhesion control.
  • The findings suggest potential implications for tissue homeostasis and oncogenesis, given the links between TGF-beta, GTPases, and cadherins in cancer metastasis.

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