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PMID: 17639085 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Genes & development ·Vol. 21 ·No. 14 ·2007-07-15 ·Pages 1817-31

Ogata S, Morokuma J, Hayata T, Kolle G, Niehrs C, Ueno N, Cho KW

Abstract

The molecular mechanisms governing the cell behaviors underlying morphogenesis remain a major focus of research in both developmental biology and cancer biology. TGF-beta ligands control cell fate specification via Smad-mediated signaling. However, their ability to guide cellular morphogenesis in a variety of biological contexts is poorly understood. We report on the discovery of a novel TGF-beta signaling-mediated cellular morphogenesis occurring during vertebrate gastrulation. Activin/nodal members of the TGF-beta superfamily induce the expression of two genes regulating cell adhesion during gastrulation: Fibronectin Leucine-rich Repeat Transmembrane 3 (FLRT3), a type I transmembrane protein containing extracellular leucine-rich repeats, and the small GTPase Rnd1. FLRT3 and Rnd1 interact physically and modulate cell adhesion during embryogenesis by controlling cell surface levels of cadherin through a dynamin-dependent endocytosis pathway. Our model suggests that cell adhesion can be dynamically regulated by sequestering cadherin through internalization, and subsequent redeploying internalized cadherin to the cell surface as needed. As numerous studies have linked aberrant expression of small GTPases, adhesion molecules such as cadherins, and TGF-beta signaling to oncogenesis and metastasis, it is tempting to speculate that this FLRT3/Rnd1/cadherin pathway might also control cell behavior and morphogenesis in adult tissue homeostasis.

MeSH Terms
Activins/metabolism Animals Base Sequence Cadherins/metabolism Cell Adhesion DNA, Complementary/genetics Endocytosis Gene Expression Regulation, Developmental In Situ Hybridization Membrane Proteins/genetics,metabolism Morphogenesis Mutation Nodal Protein Phenotype Receptors, Fibroblast Growth Factor/metabolism Signal Transduction Transforming Growth Factor beta/metabolism Xenopus/embryology,genetics,metabolism Xenopus Proteins/genetics,metabolism rho GTP-Binding Proteins/genetics,metabolism
Chemicals
Cadherins DNA, Complementary FLRT3 protein, Xenopus Membrane Proteins Nodal Protein Receptors, Fibroblast Growth Factor Rnd1 protein, Xenopus Transforming Growth Factor beta Xenopus Proteins Activins rho GTP-Binding Proteins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Ogata Souichi
Department of Developmental and Cell Biology, Developmental Biology Center, University of California at Irvine, Irvine, California 92697, USA.
Morokuma Junji
Hayata Tadayoshi
Kolle Gabriel
Niehrs Christof
Ueno Naoto
Cho Ken W Y
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1541807
Published
2007-07-15
Pages
1817-31
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC1920175
Subset
IM
Grants
NICHD NIH HHS · R01 HD029507 · United States
NICHD NIH HHS · HD29507 · United States
External Links
PubMed source DOI: 10.1101/gad.1541807 PMC Full Text View journal details
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