Bio-techne(R&D Systems)货号4645-

Bio-techne(R&D Systems)货号4645-RS-100现货Recombinant Human R-Spondin 1 Protein上海睿安生物13611631389

Background: R-Spondin 1

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 shares ~40% amino acid (aa) identity with three other R-Spondin family members (1, 2). All R-Spondins regulate Wnt/ beta-Catenin signaling but have distinct expression patterns (1-3). R-Spondin 1 competes with the Wnt antagonist DKK-1 for binding to the Wnt co-receptors, Kremen and LRP-6, reducing their DKK-1-mediated internalization (4). However, reports are mixed on whether R-Spondin 1 binds LRP-6 directly (4-6). R-Spondin 1 is expressed in early development at the roof plate boundary and is thought to contribute to dorsal neural tube development (3, 7). 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 (7, 8). Mutations in R-Spondin 1 are also linked with palmoplantar keratoderma, abnormal thickening of the skin on the palms of the hands and soles of the feet (7, 8). Postnatally, R-Spondin 1 is expressed by neuroendocrine cells in the intestine, adrenal gland and pancreas, and by epithelia in kidney and prostate (9). Injection of recombinant R-Spondin 1 in mice causes activation of beta-catenin and proliferation of intestinal crypt epithelial cells, and ameliorates experimental colitis (9, 10). Interest in R-Spondin 1 as a cell culture supplement has grown with the expansion of the organoid field. R-Spondin 1 is widely used in organoid cell culture workflows as a vital component that promotes both growth and survival of 3D organoids (11).

Structurally similar to other R-Spondins, R-Spondin 1 contains two adjacent cysteine-rich furin-like domains (aa 34-135) with one potential N-glycosylation site, 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, 12). A putative nuclear localization signal at the C-terminus may allow some expression in the nucleus (13). Potential isoforms of 200 and 236 aa have an alternate, shorter N-terminus or are missing aa 146-208, respectively (14). Over aa 21-263, human R-Spondin 1 shares 89%, 87%, 92%, 91%, 91% and 89% aa identity with mouse, rat, horse, dog, goat, and cow RSPO-1, respectively.

References:

1. Chen, J-Z. et al. (2002) Mol. Biol. Rep. 29:287.
2. Kim, K.-A. et al. (2006) Cell Cycle 5:23.
3. Nam, J.-S. et al. (2007) Gene Expr. Patterns 7:306.
4. Binnerts, M.E. et al. (2007) Proc. Natl. Acad. Sci. USA 104:14700.
5. Nam, J.-S. et al. (2006) J. Biol. Chem. 281:13247.
6. Wei, Q. et al. (2007) J. Biol. Chem. 282:15903.
7. Kamata, T. et al. (2004) Biochim. Biophys. Acta 1676:51.
8. Parma, P. et al. (2006) Nat. Genet. 38:1304.
9. Kim, K.-A. et al. (2005) Science 309:1256.
10. Zhao, J. et al. (2007) Gastroenterology 132:1331.
11. Drost and Clevers. (2018) Nature Reviews Cancer 18:407.
12. Kazanskaya, O. et al. (2004) Dev. Cell 7:525.
13. Tomaselli, S. et al. (2008) Hum. Mutat. 29:220.
14. UniProt # Q2MKA7.

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