| First Author | Haddick PC | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 1 | Pages | e84823 |
| PubMed ID | 24400119 | Mgi Jnum | J:212572 |
| Mgi Id | MGI:5581781 | Doi | 10.1371/journal.pone.0084823 |
| Citation | Haddick PC, et al. (2014) Defining the ligand specificity of the deleted in colorectal cancer (DCC) receptor. PLoS One 9(1):e84823 |
| abstractText | The growth and guidance of many axons in the developing nervous system require Netrin-mediated activation of Deleted in Colorectal Cancer (DCC) and other still unknown signaling cues. Commissural axon guidance defects are more severe in DCC mutant mice than Netrin-1 mutant mice, suggesting additional DCC activating signals besides Netrin-1 are involved in proper axon growth. Here we report that interaction screens on extracellular protein microarrays representing over 1,000 proteins uniquely identified Cerebellin 4 (CBLN4), a member of the C1q-tumor necrosis factor (TNF) family, and Netrin-1 as extracellular DCC-binding partners. Immunofluorescence and radio-ligand binding studies demonstrate that Netrin-1 competes with CBLN4 binding at an overlapping site within the membrane-proximal fibronectin domains (FN) 4-6 of DCC and binds with approximately 5-fold higher affinity. CBLN4 also binds to the DCC homolog, Neogenin-1 (NEO1), but with a lower affinity compared to DCC. CBLN4-null mice did not show a defect in commissural axons of the developing spinal cord but did display a transient increase in the number of wandering axons in the brachial plexus, consistent with a role in axon guidance. Overall, the data solidifies CBLN4 as a bona fide DCC ligand and strengthens its implication in axon guidance. |
