Villin 1

Villin 1 (VIL1) is an actin-binding protein found in the brush border of epithelial cells lining the small intestine and kidney proximal tubules, as well as in some other cell types, including leukocytes. It is encoded by the VIL1 gene in humans. Villin 1 plays a crucial role in the organization and dynamics of the actin cytoskeleton, particularly in the formation and maintenance of microvilli.

Function:

Villin 1's primary function is to regulate actin filament assembly, bundling, and severing. It contains several domains that contribute to these activities:

• Headpiece: This domain binds to actin filaments and contributes to bundling.
• Core Domain: This region is responsible for calcium-regulated actin-severing activity. In the presence of high calcium concentrations, villin 1 can sever actin filaments, leading to their depolymerization. Under low calcium conditions, it promotes actin filament bundling and stabilization.
• N-terminal Cap Site: This domain is important for membrane association.

These activities allow villin 1 to dynamically control the structure of microvilli, responding to cellular signals and environmental changes. It facilitates the rapid remodeling of the actin cytoskeleton necessary for cell motility, adhesion, and absorption.

Structure:

Villin 1 is a monomeric protein with a molecular weight of approximately 92.5 kDa. Its structure consists of a large core domain, a headpiece domain, and a smaller N-terminal cap site. The core domain is composed of several gelsolin-like repeats. The headpiece is a globular domain that provides additional actin-binding sites.

Tissue Distribution:

Villin 1 is highly expressed in tissues with absorptive functions, such as the intestinal epithelium and kidney tubules. Lower levels of expression are found in other cell types. Its localization to the apical brush border of epithelial cells is essential for microvilli formation and function.

Clinical Significance:

Mutations in the VIL1 gene are rare, but alterations in villin 1 expression and function have been implicated in various pathological conditions, including:

• Cancer: Villin 1 expression is often altered in certain types of cancer, such as colorectal cancer. Changes in its expression can affect cell motility, invasion, and metastasis.
• Celiac Disease: Altered villin 1 expression and function have been observed in patients with celiac disease, potentially contributing to the intestinal damage associated with the condition.
• Inflammatory Bowel Disease (IBD): Villin 1 may play a role in the pathogenesis of IBD by influencing the integrity of the intestinal epithelial barrier.

Interactions:

Villin 1 interacts with various proteins, including:

• Actin: The primary interaction partner, mediating actin filament bundling, severing, and capping.
• Phosphoinositides: These lipids can modulate villin 1 activity and localization.
• Other Cytoskeletal Proteins: Villin 1 interacts with other cytoskeletal components to regulate cell morphology and motility.