VE-cadherin acts as a molecular gatekeeper in the circulatory system. This protein is found exclusively in endothelial cells, which form the inner lining of blood vessels. It functions like a molecular glue, tightly sealing the gaps between these cells. This precise control over the vessel lining is important for maintaining internal balance and proper blood flow.
The Architecture of VE-Cadherin
VE-cadherin, a cell adhesion molecule of the cadherin family, is expressed on the surface of endothelial cells, forming connections vital for vessel integrity. The protein has distinct regions, each with a specialized role.
Its extracellular domain extends outside the cell, binding with VE-cadherin molecules on an adjacent endothelial cell. This creates a strong cell-to-cell link, much like interlocking fingers. A transmembrane segment anchors the protein within the cell membrane. The cytoplasmic tail, located inside the cell, connects to the actin cytoskeleton, providing structural support.
Guardian of the Vasculature
The primary function of VE-cadherin is to maintain the tight sealing of the endothelial barrier, which is necessary for healthy blood vessels. Connections formed by VE-cadherin between neighboring endothelial cells create adherens junctions. These junctions hold the cells together, regulating vascular permeability, which dictates what substances can pass from the bloodstream into surrounding tissues.
Controlling this passage is important for various bodily functions. The barrier prevents leakage of fluids and large proteins from the blood, helping maintain stable blood pressure within vessels. It also prevents swelling, or edema, in healthy tissues by ensuring fluid remains largely confined to the circulatory system. This regulated barrier function represents VE-cadherin’s steady-state role.
Role in Dynamic Vascular Processes
While VE-cadherin maintains a tight barrier, its connections are also capable of controlled, temporary disassembly. During inflammation, the loosening of these junctions allows white blood cells to temporarily squeeze between endothelial cells and migrate out of the bloodstream. This enables immune cells to reach the site of inflammation.
A similar controlled adjustment of VE-cadherin connections occurs during angiogenesis, the process of forming new blood vessels. For new vessels to form, endothelial cells must migrate and rearrange themselves. This requires the temporary disassembly of VE-cadherin junctions to allow individual cells to move, followed by their reassembly as new vessel structures are formed. This dynamic regulation is important for processes like wound healing and tissue growth, demonstrating the protein’s flexibility.
When the Barrier Fails
Dysfunction of the VE-cadherin barrier can lead to significant pathological consequences, impacting various aspects of health. When the barrier opens excessively, it results in conditions characterized by fluid leakage from blood vessels. For example, severe and widespread edema, or fluid buildup, can occur throughout the body. In the lungs, this uncontrolled leakage is a major contributing factor to acute respiratory distress syndrome (ARDS), a life-threatening condition where fluid floods the air sacs, impairing oxygen exchange.
The disruption of VE-cadherin junctions also plays a significant role in the spread of cancer, a process known as metastasis. Tumor cells can exploit the dynamic nature of these junctions to invade the bloodstream, a step called intravasation. Once in circulation, these cells can then disrupt VE-cadherin connections at distant sites to exit the bloodstream, a process called extravasation. This allows them to establish new tumors in other parts of the body, highlighting why VE-cadherin is a molecule of great interest for targeted therapeutic strategies in disease management.