Crosstalk Between Reticular Adherens Junctions and Platelet Endothelial Cell Adhesion Molecule-1 Regulates Endothelial Barrier Function

Laura Fernandez-Martin; Beatriz Marcos-Ramiro; Carolina L. Bigarella; Mariona Graupera; Robert J. Cain; Natalia Reglero-Real; Anais Jimenez; Eva Cernuda-Morollon; Isabel Correas; Susan Cox; Anne J. Ridley; Jaime Millan

doi:10.1161/ATVBAHA.112.252080

Crosstalk Between Reticular Adherens Junctions and Platelet Endothelial Cell Adhesion Molecule-1 Regulates Endothelial Barrier Function

Laura Fernandez-Martin, Beatriz Marcos-Ramiro, Carolina L. Bigarella, Mariona Graupera, Robert J. Cain, Natalia Reglero-Real, Anais Jimenez, Eva Cernuda-Morollon, Isabel Correas, Susan Cox, Anne J. Ridley, Jaime Millan

Research output: Contribution to journal › Article › peer-review

60 Citations (Scopus)

Abstract

Objective-Endothelial cells provide a barrier between the blood and tissues, which is reduced during inflammation to allow selective passage of molecules and cells. Adherens junctions (AJ) play a central role in regulating this barrier. We aim to investigate the role of a distinctive 3-dimensional reticular network of AJ found in the endothelium.

Methods and Results-In endothelial AJ, vascular endothelial-cadherin recruits the cytoplasmic proteins beta-catenin and p120-catenin. beta-catenin binds to alpha-catenin, which links AJ to actin filaments. AJ are usually described as linear structures along the actin-rich intercellular contacts. Here, we show that these AJ components can also be organized in reticular domains that contain low levels of actin. Reticular AJ are localized in areas where neighboring cells overlap and encompass the cell adhesion receptor platelet endothelial cell adhesion molecule-1 (PECAM-1). Superresolution microscopy revealed that PECAM-1 forms discrete structures distinct from and distributed along AJ, within the voids of reticular domains. Inflammatory tumor necrosis factor-alpha increases permeability by mechanisms that are independent of actomyosin-mediated tension and remain incompletely understood. Reticular AJ, but not actin-rich linear AJ, were disorganized by tumor necrosis factor-alpha. This correlated with PECAM-1 dispersal from cell borders. PECAM-1 inhibition with blocking antibodies or small interfering RNA specifically disrupted reticular AJ, leaving linear AJ intact. This disruption recapitulated typical tumor necrosis factor-alpha-induced alterations of barrier function, including increased beta-catenin phosphorylation, without altering the actomyosin cytoskeleton.

Conclusion-We propose that reticular AJ act coordinately with PECAM-1 to maintain endothelial barrier function in regions of low actomyosin-mediated tension. Selective disruption of reticular AJ contributes to permeability increase in response to tumor necrosis factor-alpha. (Arterioscler Thromb Vasc Biol. 2012;32:e90-102.)

Original language	English
Pages (from-to)	E90-U141
Number of pages	36
Journal	Arteriosclerosis, Thrombosis, and Vascular Biology
Volume	32
Issue number	8
Early online date	21 Jun 2012
DOIs	https://doi.org/10.1161/ATVBAHA.112.252080
Publication status	Published - Aug 2012

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Fernandez-Martin, L., Marcos-Ramiro, B., Bigarella, C. L., Graupera, M., Cain, R. J., Reglero-Real, N., Jimenez, A., Cernuda-Morollon, E., Correas, I., Cox, S., Ridley, A. J., & Millan, J. (2012). Crosstalk Between Reticular Adherens Junctions and Platelet Endothelial Cell Adhesion Molecule-1 Regulates Endothelial Barrier Function. Arteriosclerosis, Thrombosis, and Vascular Biology, 32(8), E90-U141. https://doi.org/10.1161/ATVBAHA.112.252080

@article{f31c78d01ee64d4ca004f3f52cd24d81,

title = "Crosstalk Between Reticular Adherens Junctions and Platelet Endothelial Cell Adhesion Molecule-1 Regulates Endothelial Barrier Function",

abstract = "Objective-Endothelial cells provide a barrier between the blood and tissues, which is reduced during inflammation to allow selective passage of molecules and cells. Adherens junctions (AJ) play a central role in regulating this barrier. We aim to investigate the role of a distinctive 3-dimensional reticular network of AJ found in the endothelium.Methods and Results-In endothelial AJ, vascular endothelial-cadherin recruits the cytoplasmic proteins beta-catenin and p120-catenin. beta-catenin binds to alpha-catenin, which links AJ to actin filaments. AJ are usually described as linear structures along the actin-rich intercellular contacts. Here, we show that these AJ components can also be organized in reticular domains that contain low levels of actin. Reticular AJ are localized in areas where neighboring cells overlap and encompass the cell adhesion receptor platelet endothelial cell adhesion molecule-1 (PECAM-1). Superresolution microscopy revealed that PECAM-1 forms discrete structures distinct from and distributed along AJ, within the voids of reticular domains. Inflammatory tumor necrosis factor-alpha increases permeability by mechanisms that are independent of actomyosin-mediated tension and remain incompletely understood. Reticular AJ, but not actin-rich linear AJ, were disorganized by tumor necrosis factor-alpha. This correlated with PECAM-1 dispersal from cell borders. PECAM-1 inhibition with blocking antibodies or small interfering RNA specifically disrupted reticular AJ, leaving linear AJ intact. This disruption recapitulated typical tumor necrosis factor-alpha-induced alterations of barrier function, including increased beta-catenin phosphorylation, without altering the actomyosin cytoskeleton.Conclusion-We propose that reticular AJ act coordinately with PECAM-1 to maintain endothelial barrier function in regions of low actomyosin-mediated tension. Selective disruption of reticular AJ contributes to permeability increase in response to tumor necrosis factor-alpha. (Arterioscler Thromb Vasc Biol. 2012;32:e90-102.)",

author = "Laura Fernandez-Martin and Beatriz Marcos-Ramiro and Bigarella, {Carolina L.} and Mariona Graupera and Cain, {Robert J.} and Natalia Reglero-Real and Anais Jimenez and Eva Cernuda-Morollon and Isabel Correas and Susan Cox and Ridley, {Anne J.} and Jaime Millan",

year = "2012",

month = aug,

doi = "10.1161/ATVBAHA.112.252080",

language = "English",

volume = "32",

pages = "E90--U141",

journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",

issn = "1079-5642",

publisher = "Lippincott Williams and Wilkins",

number = "8",

}

Fernandez-Martin, L, Marcos-Ramiro, B, Bigarella, CL, Graupera, M, Cain, RJ, Reglero-Real, N, Jimenez, A, Cernuda-Morollon, E, Correas, I, Cox, S , Ridley, AJ & Millan, J 2012, 'Crosstalk Between Reticular Adherens Junctions and Platelet Endothelial Cell Adhesion Molecule-1 Regulates Endothelial Barrier Function', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 32, no. 8, pp. E90-U141. https://doi.org/10.1161/ATVBAHA.112.252080

Crosstalk Between Reticular Adherens Junctions and Platelet Endothelial Cell Adhesion Molecule-1 Regulates Endothelial Barrier Function. / Fernandez-Martin, Laura; Marcos-Ramiro, Beatriz; Bigarella, Carolina L. et al.
In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 32, No. 8, 08.2012, p. E90-U141.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Crosstalk Between Reticular Adherens Junctions and Platelet Endothelial Cell Adhesion Molecule-1 Regulates Endothelial Barrier Function

AU - Fernandez-Martin, Laura

AU - Marcos-Ramiro, Beatriz

AU - Bigarella, Carolina L.

AU - Graupera, Mariona

AU - Cain, Robert J.

AU - Reglero-Real, Natalia

AU - Jimenez, Anais

AU - Cernuda-Morollon, Eva

AU - Correas, Isabel

AU - Cox, Susan

AU - Ridley, Anne J.

AU - Millan, Jaime

PY - 2012/8

Y1 - 2012/8

N2 - Objective-Endothelial cells provide a barrier between the blood and tissues, which is reduced during inflammation to allow selective passage of molecules and cells. Adherens junctions (AJ) play a central role in regulating this barrier. We aim to investigate the role of a distinctive 3-dimensional reticular network of AJ found in the endothelium.Methods and Results-In endothelial AJ, vascular endothelial-cadherin recruits the cytoplasmic proteins beta-catenin and p120-catenin. beta-catenin binds to alpha-catenin, which links AJ to actin filaments. AJ are usually described as linear structures along the actin-rich intercellular contacts. Here, we show that these AJ components can also be organized in reticular domains that contain low levels of actin. Reticular AJ are localized in areas where neighboring cells overlap and encompass the cell adhesion receptor platelet endothelial cell adhesion molecule-1 (PECAM-1). Superresolution microscopy revealed that PECAM-1 forms discrete structures distinct from and distributed along AJ, within the voids of reticular domains. Inflammatory tumor necrosis factor-alpha increases permeability by mechanisms that are independent of actomyosin-mediated tension and remain incompletely understood. Reticular AJ, but not actin-rich linear AJ, were disorganized by tumor necrosis factor-alpha. This correlated with PECAM-1 dispersal from cell borders. PECAM-1 inhibition with blocking antibodies or small interfering RNA specifically disrupted reticular AJ, leaving linear AJ intact. This disruption recapitulated typical tumor necrosis factor-alpha-induced alterations of barrier function, including increased beta-catenin phosphorylation, without altering the actomyosin cytoskeleton.Conclusion-We propose that reticular AJ act coordinately with PECAM-1 to maintain endothelial barrier function in regions of low actomyosin-mediated tension. Selective disruption of reticular AJ contributes to permeability increase in response to tumor necrosis factor-alpha. (Arterioscler Thromb Vasc Biol. 2012;32:e90-102.)

AB - Objective-Endothelial cells provide a barrier between the blood and tissues, which is reduced during inflammation to allow selective passage of molecules and cells. Adherens junctions (AJ) play a central role in regulating this barrier. We aim to investigate the role of a distinctive 3-dimensional reticular network of AJ found in the endothelium.Methods and Results-In endothelial AJ, vascular endothelial-cadherin recruits the cytoplasmic proteins beta-catenin and p120-catenin. beta-catenin binds to alpha-catenin, which links AJ to actin filaments. AJ are usually described as linear structures along the actin-rich intercellular contacts. Here, we show that these AJ components can also be organized in reticular domains that contain low levels of actin. Reticular AJ are localized in areas where neighboring cells overlap and encompass the cell adhesion receptor platelet endothelial cell adhesion molecule-1 (PECAM-1). Superresolution microscopy revealed that PECAM-1 forms discrete structures distinct from and distributed along AJ, within the voids of reticular domains. Inflammatory tumor necrosis factor-alpha increases permeability by mechanisms that are independent of actomyosin-mediated tension and remain incompletely understood. Reticular AJ, but not actin-rich linear AJ, were disorganized by tumor necrosis factor-alpha. This correlated with PECAM-1 dispersal from cell borders. PECAM-1 inhibition with blocking antibodies or small interfering RNA specifically disrupted reticular AJ, leaving linear AJ intact. This disruption recapitulated typical tumor necrosis factor-alpha-induced alterations of barrier function, including increased beta-catenin phosphorylation, without altering the actomyosin cytoskeleton.Conclusion-We propose that reticular AJ act coordinately with PECAM-1 to maintain endothelial barrier function in regions of low actomyosin-mediated tension. Selective disruption of reticular AJ contributes to permeability increase in response to tumor necrosis factor-alpha. (Arterioscler Thromb Vasc Biol. 2012;32:e90-102.)

U2 - 10.1161/ATVBAHA.112.252080

DO - 10.1161/ATVBAHA.112.252080

M3 - Article

SN - 1079-5642

VL - 32

SP - E90-U141

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

IS - 8

ER -

Crosstalk Between Reticular Adherens Junctions and Platelet Endothelial Cell Adhesion Molecule-1 Regulates Endothelial Barrier Function

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