Function

Netrin receptors are cell surface proteins which bind netrins. Netrins direct cell and axon migration during development.

  • Netrin attraction is mediated through DCC (Deleted in Colorectal Cancer) receptors while netrin repulsion is mediated through the UNC-5 receptor[1], [2] .
  • UNC-5B receptor or UNC-5H2 is a repulsive netrin recptor in endothelial cells controlling morphogenesis of the vascular system[3].
  • UNC-5D receptor may mediate the effect of netrin-4 on cortical cell survival[4].

Disease

DCC gene is deleted in most colorectal cancer patients as well as in other cancers[5].

Structural highlights

Netrin DCC receptor extracellular domain contains 4 Ig repeats followed by 6 type III fibronectin repeats. Netrin UNC-5 receptor extracellular domain contains 2 Ig repeats followed by 2 type I thrombospondin repeats.


Glycosylated human netrin receptor DCC fibronectin type V-VI domains (green) complex with neutrin-1 (grey), sulfate, Ca+2 and Cl-1 ions (PDB code 4urt)

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3D Structures of netrin receptor3D Structures of netrin receptor

Updated on 16-July-2024

ReferencesReferences

  1. Moore SW, Tessier-Lavigne M, Kennedy TE. Netrins and their receptors. Adv Exp Med Biol. 2007;621:17-31. doi: 10.1007/978-0-387-76715-4_2. PMID:18269208 doi:http://dx.doi.org/10.1007/978-0-387-76715-4_2
  2. Keleman K, Dickson BJ. Short Neuron. 2001 Nov 20;32(4):605-17. PMID:11719202 doi:10.1016/s0896-6273(01)00505-0
  3. Lu X, Le Noble F, Yuan L, Jiang Q, De Lafarge B, Sugiyama D, Bréant C, Claes F, De Smet F, Thomas JL, Autiero M, Carmeliet P, Tessier-Lavigne M, Eichmann A. The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system. Nature. 2004 Nov 11;432(7014):179-86. PMID:15510105 doi:10.1038/nature03080
  4. Takemoto M, Hattori Y, Zhao H, Sato H, Tamada A, Sasaki S, Nakajima K, Yamamoto N. Laminar and areal expression of unc5d and its role in cortical cell survival. Cereb Cortex. 2011 Aug;21(8):1925-34. PMID:21216843 doi:10.1093/cercor/bhq265
  5. Mehlen P, Llambi F. Role of netrin-1 and netrin-1 dependence receptors in colorectal cancers. Br J Cancer. 2005 Jul 11;93(1):1-6. PMID:15956977 doi:http://dx.doi.org/10.1038/sj.bjc.6602656

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