VANGL2
VANGL2 is a gene in humans that encodes a transmembrane protein. It plays a crucial role in planar cell polarity (PCP), a fundamental process in development that establishes coordinated cellular orientation within the plane of an epithelium.
Function:
The VANGL2 protein is a core component of the non-canonical Wnt signaling pathway, specifically the PCP pathway. This pathway is essential for processes such as neural tube closure, cochlear hair cell orientation in the inner ear, and proper orientation of stereocilia in sensory organs. VANGL2 acts as a transmembrane protein that interacts with other core PCP proteins, including Frizzled, Dishevelled, Strabismus/Vangl, and Prickle, to form complexes that transmit polarity information across cells. These complexes localize asymmetrically within the cell membrane, generating a polarized distribution of PCP proteins. This polarized distribution drives the coordinated alignment of cells within the tissue.
Structure:
VANGL2 is a four-pass transmembrane protein. It possesses several extracellular and intracellular domains that mediate interactions with other proteins involved in PCP signaling. The exact structure and binding affinities with its interacting partners are areas of ongoing research.
Clinical Significance:
Mutations in the VANGL2 gene have been linked to neural tube defects, including spina bifida and craniorachischisis. These defects occur due to a failure of the neural tube to close properly during embryonic development, a process that relies heavily on the proper function of the PCP pathway. Furthermore, variations in VANGL2 have also been associated with other developmental disorders involving disruptions in planar cell polarity. Research suggests a possible role for VANGL2 in the development of certain cancers, although the specific mechanisms are still being investigated.
Interactions:
VANGL2 interacts with several other proteins within the PCP pathway, including:
- Frizzled (FZD) receptors
- Dishevelled (DVL) proteins
- Prickle (PK) proteins
- Strabismus/Vangl (STBM/VANGL1) proteins
These interactions are essential for the establishment and maintenance of planar cell polarity.