Rho GEFs in endothelial junctions effector selectivity and signaling integration determine junctional response

Research output: Contribution to journalComment/debate

4 Citations (Scopus)

Abstract

Rho GTPases are cytoskeleton-regulating proteins that mediate the formation of intercellular junctions. Their localized activation by Rho GEFs (guanine-nucleotide exchange factors) and the selective activation of downstream effectors have emerged as areas of active research in the cell adhesion field. We reported recently that the Rho-specific GEFs Syx (Synectin-binding RhoA exchange factor) and TEM4 (Tumor Endothelial Marker 4) are both essential for endothelial junction maturation and barrier function. Syx is recruited to cell contacts via its C-terminal PDZ binding motif and it's interaction with Mupp1 and the Crumbs polarity complex, while the junctional localization of TEM4 requires it's N-terminal domain and interaction with the cadherin-catenin complex. Our findings support multiple roles for RhoA in junction formation and maintenance. They also suggest that selective coupling of RhoA activation to Dia1 and/or ROCK signaling is critical for determining endothelial junction integrity.

Original languageEnglish (US)
JournalTissue Barriers
Volume1
Issue number5
StatePublished - 2013

Fingerprint

Rho Guanine Nucleotide Exchange Factors
Tumor Biomarkers
Chemical activation
Catenins
rho GTP-Binding Proteins
Intercellular Junctions
Tumors
Cadherins
Cytoskeleton
Cell Adhesion
Guanine Nucleotide Exchange Factors
Cell adhesion
Maintenance
Research
Proteins

Keywords

  • Adhesion
  • Cadherin
  • Cell junctions
  • Endothelial
  • Epithelial
  • GEFs
  • References
  • Rho GTPases

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Histology

Cite this

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title = "Rho GEFs in endothelial junctions effector selectivity and signaling integration determine junctional response",
abstract = "Rho GTPases are cytoskeleton-regulating proteins that mediate the formation of intercellular junctions. Their localized activation by Rho GEFs (guanine-nucleotide exchange factors) and the selective activation of downstream effectors have emerged as areas of active research in the cell adhesion field. We reported recently that the Rho-specific GEFs Syx (Synectin-binding RhoA exchange factor) and TEM4 (Tumor Endothelial Marker 4) are both essential for endothelial junction maturation and barrier function. Syx is recruited to cell contacts via its C-terminal PDZ binding motif and it's interaction with Mupp1 and the Crumbs polarity complex, while the junctional localization of TEM4 requires it's N-terminal domain and interaction with the cadherin-catenin complex. Our findings support multiple roles for RhoA in junction formation and maintenance. They also suggest that selective coupling of RhoA activation to Dia1 and/or ROCK signaling is critical for determining endothelial junction integrity.",
keywords = "Adhesion, Cadherin, Cell junctions, Endothelial, Epithelial, GEFs, References, Rho GTPases",
author = "Ngok, {Siu P.} and Anastasiadis, {Panagiotis Z}",
year = "2013",
language = "English (US)",
volume = "1",
journal = "Tissue Barriers",
issn = "2168-8362",
publisher = "Taylor and Francis Ltd.",
number = "5",

}

TY - JOUR

T1 - Rho GEFs in endothelial junctions effector selectivity and signaling integration determine junctional response

AU - Ngok, Siu P.

AU - Anastasiadis, Panagiotis Z

PY - 2013

Y1 - 2013

N2 - Rho GTPases are cytoskeleton-regulating proteins that mediate the formation of intercellular junctions. Their localized activation by Rho GEFs (guanine-nucleotide exchange factors) and the selective activation of downstream effectors have emerged as areas of active research in the cell adhesion field. We reported recently that the Rho-specific GEFs Syx (Synectin-binding RhoA exchange factor) and TEM4 (Tumor Endothelial Marker 4) are both essential for endothelial junction maturation and barrier function. Syx is recruited to cell contacts via its C-terminal PDZ binding motif and it's interaction with Mupp1 and the Crumbs polarity complex, while the junctional localization of TEM4 requires it's N-terminal domain and interaction with the cadherin-catenin complex. Our findings support multiple roles for RhoA in junction formation and maintenance. They also suggest that selective coupling of RhoA activation to Dia1 and/or ROCK signaling is critical for determining endothelial junction integrity.

AB - Rho GTPases are cytoskeleton-regulating proteins that mediate the formation of intercellular junctions. Their localized activation by Rho GEFs (guanine-nucleotide exchange factors) and the selective activation of downstream effectors have emerged as areas of active research in the cell adhesion field. We reported recently that the Rho-specific GEFs Syx (Synectin-binding RhoA exchange factor) and TEM4 (Tumor Endothelial Marker 4) are both essential for endothelial junction maturation and barrier function. Syx is recruited to cell contacts via its C-terminal PDZ binding motif and it's interaction with Mupp1 and the Crumbs polarity complex, while the junctional localization of TEM4 requires it's N-terminal domain and interaction with the cadherin-catenin complex. Our findings support multiple roles for RhoA in junction formation and maintenance. They also suggest that selective coupling of RhoA activation to Dia1 and/or ROCK signaling is critical for determining endothelial junction integrity.

KW - Adhesion

KW - Cadherin

KW - Cell junctions

KW - Endothelial

KW - Epithelial

KW - GEFs

KW - References

KW - Rho GTPases

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M3 - Comment/debate

VL - 1

JO - Tissue Barriers

JF - Tissue Barriers

SN - 2168-8362

IS - 5

ER -