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 language | English (US) |
|---|---|
| Journal | Tissue Barriers |
| Volume | 1 |
| Issue number | 5 |
| State | Published - 2013 |
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Keywords
- Adhesion
- Cadherin
- Cell junctions
- Endothelial
- Epithelial
- GEFs
- References
- Rho GTPases
ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Histology
Cite this
Rho GEFs in endothelial junctions effector selectivity and signaling integration determine junctional response. / Ngok, Siu P.; Anastasiadis, Panagiotis Z.
In: Tissue Barriers, Vol. 1, No. 5, 2013.Research output: Contribution to journal › Comment/debate
}
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
UR - http://www.scopus.com/inward/record.url?scp=84922249070&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84922249070&partnerID=8YFLogxK
M3 - Comment/debate
AN - SCOPUS:84922249070
VL - 1
JO - Tissue Barriers
JF - Tissue Barriers
SN - 2168-8362
IS - 5
ER -