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Beschreibung

Cartilage acidic protein 1 (UniProt: Q8R555, also known as 68 kDa chondrocyte-expressed protein, CEP-68, ASPIC, Protein CRTAC1-B, Lateral olfactory tract usher substance, LOTUS) is encoded by the Crtac1 (also known as Aspic1, Cep68) gene (Gene ID: 72832) in murine species. LOTUS is synthesized with a signal peptide (aa 1-28), which is subsequently cleaved off to generate the mature form (aa 29-646). It is a membrane-bound and/or secreted protein that serves as an endogenous Nogo receptor-1 (NgR1) antagonist. It is shown to contribute to the formation of the lateral olfactory tract (LOT) axonal bundle. Endogenous Nogo-A signaling through NgR1 is shown to induce axonal branching. Developmental up-regulation of Nogo-A promotes collateral formation of the LOT during the late development period. It has been reported that axon growth inhibitors, which include Nogo proteins, myelin-associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMgp), and B lymphocyte stimulator (BLyS), bind to NgR1 and restrict functional recovery after damage to the adult central nervous system. LOTUS blocks the binding of these ligands to NgR1 and suppresses growth cone collapse. LOTUS knockout mice show significantly increased collateral branches of axons in the LOT. On the other hand, this branching is diminished in NgR1 knockout mice. A simultaneous loss of LOTUS and NgR1 is reported to rescue the abnormal increase in axonal branches. (Ref.: Iketani, M., et al. (2016). Sci. Rep. 6, 39586, Kurihara, Y., et al. (2014). Mol. Cell. Neurosci. 61, 211-218).