Occludin
Occludin
Occludin is an integral membrane protein that plays a critical role in the formation and maintenance of tight junctions in epithelial and endothelial cells. Tight junctions are essential for maintaining the selective permeability barrier of epithelial layers, which separates different tissue compartments and regulates the passage of ions, molecules, and cells.
Structure
Occludin is a tetraspan membrane protein, meaning it spans the membrane four times. It has two extracellular loops, a short N-terminal cytoplasmic domain, and a longer C-terminal cytoplasmic domain. The C-terminal domain is involved in interactions with other tight junction proteins and the cytoskeleton, which are crucial for the stability and function of tight junctions.
Function
Occludin is a key component of the tight junction complex, which includes other proteins such as claudins, junctional adhesion molecules (JAMs), and zonula occludens (ZO) proteins. Occludin contributes to the barrier and fence functions of tight junctions, helping to regulate paracellular transport and maintain cell polarity.
Barrier Function
The barrier function of tight junctions is essential for controlling the movement of solutes and water between cells. Occludin, along with claudins, forms a seal that restricts the passage of ions and small molecules through the paracellular space.
Fence Function
The fence function of tight junctions prevents the mixing of membrane proteins and lipids between the apical and basolateral surfaces of epithelial cells, thus maintaining cell polarity. Occludin plays a role in this function by interacting with the actin cytoskeleton and other tight junction proteins.
Regulation
The expression and function of occludin are regulated by various signaling pathways, including those involving protein kinase C (PKC) and Rho GTPases. Phosphorylation of occludin can modulate its interaction with other proteins and its localization at the tight junction.
Clinical Significance
Alterations in occludin expression or function have been implicated in various pathological conditions, including inflammatory bowel disease, cancer, and stroke. In these conditions, the disruption of tight junctions can lead to increased permeability and loss of barrier function, contributing to disease progression.
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