Mouse R-Spondin 1 Alexa Fluor® 750-conjugated Antibody

R-Spondin 1 (RSPO1, Roof plate-specific Spondin 1), also known as cysteine-rich and single thrombospondin domain containing protein 3 (Cristin 3), is a 27 kDa secreted protein that belongs to the R-Spondin family (1, 2). R-Spondins share around 40% aa identity. All regulate Wnt/ beta-catenin signaling, but have distinct expression patterns (1 - 3). Like other R-spondins, R-Spondin 1 contains two adjacent cysteine-rich furin-like domains (amino acids (aa) 34 - 135) followed by a thrombospondin (TSP-1) motif (aa 147 - 207) and a region rich in basic residues (aa 211 - 263). Only the furin-like domains are needed for beta-catenin stabilization (2, 4). A putative nuclear localization signal at the C-terminus may allow some expression in the nucleus (5). R-Spondin 1 contains one potential N-glycosylation site. Over aa 21 - 209, mouse R-Spondin 1 shares 98%, 94%, 94%, 93%, 92% and 88% aa identity with rat, human, horse, cow, goat and dog RSPO-1, respectively. R-Spondin 1 is expressed in early development at the roof plate boundary and is thought to contribute to dorsal neural tube development (3, 5). In humans, rare disruptions of the R-Spondin 1 gene are associated with tendencies for XX sex reversal (phenotypic male) or hermaphroditism, indicating a role for R-Spondin 1 in gender-specific differentiation (6, 7). Disruption is also associated with palmoplantar keratosis (6, 7). Postnatally, R-Spondin 1 is expressed by neuroendocrine cells in the intestine, adrenal gland and pancreas, and by epithelia in kidney and prostate (8). Injection of recombinant R-Spondin 1 in mice causes activation of beta-catenin and proliferation of intestinal crypt epithelial cells, and ameliorates experimental colitis (8, 9). R-Spondin 1 appears to regulate Wnt/ beta-catenin by competing with the Wnt antagonist DKK-1 for binding to the Wnt co-receptor, Kremen (10). This competition reduces internalization of DKK-1/LRP-6/Kremen complexes (10). Reports differ on whether R‑Spondin 1 binds LRP-6 directly (10 - 12).