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Review
. 2021;58(2):65-91.
doi: 10.1159/000512618. Epub 2021 Jan 27.

Polarized Proteins in Endothelium and Their Contribution to Function

Abigail G Wolpe  1   2 , Claire A Ruddiman  1   3 , Phillip J Hall  1 , Brant E Isakson  4   5
Affiliations
Review

Polarized Proteins in Endothelium and Their Contribution to Function

Abigail G Wolpe et al. J Vasc Res. 2021.

Abstract

Protein localization in endothelial cells is tightly regulated to create distinct signaling domains within their tight spatial restrictions including luminal membranes, abluminal membranes, and interendothelial junctions, as well as caveolae and calcium signaling domains. Protein localization in endothelial cells is also determined in part by the vascular bed, with differences between arteries and veins and between large and small arteries. Specific protein polarity and localization is essential for endothelial cells in responding to various extracellular stimuli. In this review, we examine protein localization in the endothelium of resistance arteries, with occasional references to other vessels for contrast, and how that polarization contributes to endothelial function and ultimately whole organism physiology. We highlight the protein localization on the luminal surface, discussing important physiological receptors and the glycocalyx. The protein polarization to the abluminal membrane is especially unique in small resistance arteries with the presence of the myoendothelial junction, a signaling microdomain that regulates vasodilation, feedback to smooth muscle cells, and ultimately total peripheral resistance. We also discuss the interendothelial junction, where tight junctions, adherens junctions, and gap junctions all convene and regulate endothelial function. Finally, we address planar cell polarity, or axial polarity, and how this is regulated by mechanosensory signals like blood flow.

Keywords: Arteriole; Endothelium; Protein localization; Signaling domains.

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Conflict of interest statement

Disclosure Statement

The authors have no conflicts of interest to declare.

Figures

Figure 1.
Figure 1.. Luminal protein localization in endothelium.
The luminal membrane of the endothelium is in direct contact with the circulation. The glycocalyx, ectonucleases, immune signaling proteins and luminally-secreted proteins localize to the luminal membrane. Transverse view of resistance artery is depicted in the upper left for reference.
Figure 2.
Figure 2.. Abluminal protein localization in endothelium.
The luminal membrane of the endothelium is in direct contact with the extracellular matrix and sporadically the smooth muscle (but not larger arteries). Transverse view of resistance artery is depicted in the upper left for reference.
Figure 3.
Figure 3.. Interendothelial junction protein localization in endothelium.
The apposition of endothelium is a key area of protein localization
Figure 4.
Figure 4.. Polarization of endothelium in response to different flow environments.
Claudin-5 (green, Thermofisher 34–1600) is used to demonstrate differences in polarization of interendothelial proteins to lateral edges of the cells in a murine third order mesenteric artery with high flow (A) compared with a murine third order mesenteric vein with low flow (B). The images also highlight endothelial morphological differences in arteries versus veins: arterial endothelial cells are elongated in the direction of flow while venous endothelial cells are more rectangular in shape and resemble cultured cells. For each image, arrow indicates direction of flow, scale bar is 10μm, and nuclei are shown in blue, with endothelial nuclei oriented vertically and SMC nuclei oriented horizontally. Images were obtained with a Zeiss 880 LSM Airyscan module (40x oil objective) and are shown as Z-projections.
See this image and copyright information in PMC

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