RGMa is a repulsive guidance molecule for retinal axons.[7] Furthermore, neogenin functions as a receptor for RGM.[8] Neogenin overexpression and RGM downexpression in the developing embryonic neural tube induces apoptosis. The apoptotic activity of neogenin in the neural tube is associated with cleavage of its cytoplasmic domain by caspases.[9]
RGMA belongs to a family of repulsive guidance molecules that are (glycosylphosphatidylinositol)-linked cell-membrane-associated proteins. The three proteins, RGMa (this protein), RGMb and RGMc are 40-50% identical to each other, and share similarities in predicted protein domains and overall structure. All three RGM proteins appear capable of binding selected BMPs (bone morphogenetic proteins).[10]
RGMs may play inhibitory roles in prostate cancer by suppressing cell growth, adhesion, migration and invasion. RGMs can coordinate Smad-dependent and Smad-independent signalling of BMPs in prostate cancer and breast cancer cells.[11][12]
^Monnier PP, Sierra A, Macchi P, Deitinghoff L, Andersen JS, Mann M, Flad M, Hornberger MR, Stahl B, Bonhoeffer F, Mueller BK (September 2002). "RGM is a repulsive guidance molecule for retinal axons". Nature. 419 (6905): 392–5. doi:10.1038/nature01041. PMID12353034.
^Rajagopalan S, Deitinghoff L, Davis D, Conrad S, Skutella T, Chedotal A, Mueller BK, Strittmatter SM (August 2004). "Neogenin mediates the action of repulsive guidance molecule". Nat. Cell Biol. 6 (8): 756–62. doi:10.1038/ncb1156. PMID15258590.
^Matsunaga E, Tauszig-Delamasure S, Monnier PP, Mueller BK, Strittmatter SM, Mehlen P, Chédotal A (August 2004). "RGM and its receptor neogenin regulate neuronal survival". Nat. Cell Biol. 6 (8): 749–55. doi:10.1038/ncb1157. PMID15258591.
^Li J, Ye L, Sanders AJ, Jiang WG (March 2012). "Repulsive guidance molecule B (RGMB) plays negative roles in breast cancer by coordinating BMP signaling". J Cell Biochem. 113 (7): 2523–31. doi:10.1002/jcb.24128. PMID22415859.
^Li J, Ye L, Kynaston HG, Jiang WG (February 2012). "Repulsive guidance molecules, novel bone morphogenetic protein co-receptors, are key regulators of the growth and aggressiveness of prostate cancer cells". Int. J. Oncol. 40 (2): 544–50. doi:10.3892/ijo.2011.1251. PMID22076499.