RSPO2

RSPO2, also known as R-spondin 2, is a secreted protein that plays a crucial role in the Wnt signaling pathway. It is a member of the R-spondin family, which are known for their ability to enhance Wnt signaling by binding to leucine-rich repeat-containing G protein-coupled receptors (LGRs) 4, 5, and 6. RSPO2 specifically interacts with LGR4 and LGR5.

The primary function of RSPO2 is to potentiate the canonical Wnt/beta-catenin signaling pathway. It achieves this by forming a complex with LGR receptors and a ubiquitin ligase, such as ZNRF1 or RNFT2. This complex then targets and promotes the degradation of negative regulators of Wnt signaling, like Kremen1 and Dickkopf-1 (DKK1). By reducing the levels of these inhibitors, RSPO2 leads to an accumulation of beta-catenin in the cytoplasm, which then translocates to the nucleus to activate Wnt target genes.

RSPO2 is widely expressed during embryonic development and in adult tissues, including the skin, hair follicles, and mammary glands. It is involved in various developmental processes, such as organogenesis, tissue regeneration, and stem cell maintenance. In the context of the skin, RSPO2 is important for hair follicle development and cycling. It also plays a role in epithelial stem cell proliferation and differentiation. Aberrant RSPO2 expression has been implicated in the development of certain cancers, particularly those where Wnt signaling is dysregulated. Research is ongoing to understand the full spectrum of RSPO2's biological functions and its therapeutic potential.