| First Author | Reuten R | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 13515 | PubMed ID | 27901020 |
| Mgi Jnum | J:243168 | Mgi Id | MGI:5907798 |
| Doi | 10.1038/ncomms13515 | Citation | Reuten R, et al. (2016) Structural decoding of netrin-4 reveals a regulatory function towards mature basement membranes. Nat Commun 7:13515 |
| abstractText | Netrins, a family of laminin-related molecules, have been proposed to act as guidance cues either during nervous system development or the establishment of the vascular system. This was clearly demonstrated for netrin-1 via its interaction with the receptors DCC and UNC5s. However, mainly based on shared homologies with netrin-1, netrin-4 was also proposed to play a role in neuronal outgrowth and developmental/pathological angiogenesis via interactions with netrin-1 receptors. Here, we present the high-resolution structure of netrin-4, which shows unique features in comparison with netrin-1, and show that it does not bind directly to any of the known netrin-1 receptors. We show that netrin-4 disrupts laminin networks and basement membranes (BMs) through high-affinity binding to the laminin gamma1 chain. We hypothesize that this laminin-related function is essential for the previously described effects on axon growth promotion and angiogenesis. Our study unveils netrin-4 as a non-enzymatic extracellular matrix protein actively disrupting pre-existing BMs. |
