Structural highlights
Function[NET1_CHICK] Netrins control guidance of CNS commissural axons and peripheral motor axons. Promotes neurite outgrowth from commissural axons but acts as a chemorepellent for trochlear motor axons. These effects are mediated by distinct receptors. [NEO1_MOUSE] May be involved as a regulatory protein in the transition of undifferentiated proliferating cells to their differentiated state. May also function as a cell adhesion molecule in a broad spectrum of embryonic and adult tissues. Publication Abstract from PubMedNetrins are secreted proteins that regulate axon guidance and neuronal migration. Deleted in colorectal cancer (DCC) is a well-established netrin-1 receptor mediating attractive responses. We provide evidence that its close relative neogenin is also a functional netrin-1 receptor that acts with DCC to mediate guidance in vivo. We determined the structures of a functional netrin-1 region, alone and in complexes with neogenin or DCC. Netrin-1 has a rigid elongated structure containing two receptor-binding sites at opposite ends through which it brings together receptor molecules. The ligand/receptor complexes reveal two distinct architectures: a 2:2 heterotetramer and a continuous ligand/receptor assembly. The differences result from different lengths of the linker connecting receptor domains fibronectin type III domain 4 (FN4) and FN5, which differs among DCC and neogenin splice variants, providing a basis for diverse signaling outcomes. Neural migration. Structures of netrin-1 bound to two receptors provide insight into its axon guidance mechanism.,Xu K, Wu Z, Renier N, Antipenko A, Tzvetkova-Robev D, Xu Y, Minchenko M, Nardi-Dei V, Rajashankar KR, Himanen J, Tessier-Lavigne M, Nikolov DB Science. 2014 Jun 13;344(6189):1275-9. doi: 10.1126/science.1255149. Epub 2014, May 29. PMID:24876346[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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