RSPO2 : R-spondin 2
Description
The RSPO2 (R-spondin 2) is a protein-coding gene located on chromosome 8.
The RSPO2 gene provides instructions for making a protein called R-spondin-2. R-spondin-2 plays a role in the Wnt signaling pathway, a series of steps that affect the way cells and tissues develop. Wnt signaling is important for cell division, attachment of cells to one another (adhesion), cell movement (migration), and many other cellular activities. During early development, Wnt signaling plays a critical role in growth and development of the skeleton and other tissues. The role of R-spondin-2 is to increase Wnt signaling. Specifically, R-spondin-2 attaches (binds) to certain proteins on the surface of cells to turn off (inactivate) proteins that block the Wnt pathway.
RSPO2 activates the canonical Wnt signaling pathway by binding to LGR4, LGR5, or LGR6 receptors. This binding leads to the association of LGR4-6 with phosphorylated LRP6 and frizzled receptors, which are activated by extracellular Wnt receptors. This activation triggers the canonical Wnt signaling pathway and increases the expression of target genes. RSPO2 also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signaling by inhibiting ZNRF3, a key regulator of the Wnt signaling pathway. During embryonic development, RSPO2 plays a crucial role in limb specification by amplifying the Wnt signaling pathway independently of LGR4-6 receptors. This amplification likely occurs through RSPO2 acting as a direct antagonistic ligand to RNF43 and ZNRF3, thereby controlling the number of limbs an embryo forms.
RSPO2 is also known as CRISTIN2, HHRRD, TETAMS2.
Associated Diseases
- Tetraamelia syndrome 2
- Tetraamelia-multiple malformations syndrome
- Humerofemoral hypoplasia with radiotibial ray deficiency
- Tetra-amelia syndrome
