Keino-Masu K, Masu M, Hinck L, Leonardo E D, Chan S S, Culotti J G, Tessier-Lavigne M
Howard Hughes Medical Institute, Department of Anatomy, University of California, San Francisco 94143-0452, USA.
Cell. 1996 Oct 18;87(2):175-85. doi: 10.1016/s0092-8674(00)81336-7.
The guidance of developing axons in the nervous system is mediated partly by diffusible chemoattractants secreted by axonal target cells. Netrins are chemoattractants for commissural axons in the vertebrate spinal cord, but the mechanisms through which they produce their effects are unknown. We show that Deleted in Colorectal Cancer (DCC), a transmembrane protein of the immunoglobulin superfamily, is expressed on spinal commissural axons and possesses netrin-1-binding activity. Moreover, an antibody to DCC selectively blocks the netrin-1-dependent outgrowth of commissural axons in vitro. These results indicate that DCC is a receptor or a component of a receptor that mediates the effects of netrin-1 on commissural axons, and they complement genetic evidence for interactions between DCC and netrin homologs in C. elegans and Drosophila.
神经系统中轴突的生长导向部分是由轴突靶细胞分泌的可扩散化学引诱剂介导的。Netrins是脊椎动物脊髓中连合轴突的化学引诱剂，但其产生作用的机制尚不清楚。我们发现，结直肠癌缺失基因（DCC），一种免疫球蛋白超家族的跨膜蛋白，在脊髓连合轴突上表达并具有netrin-1结合活性。此外，一种针对DCC的抗体在体外能选择性地阻断连合轴突依赖netrin-1的生长。这些结果表明，DCC是介导netrin-1对连合轴突作用的一种受体或受体的一个组成部分，并且补充了秀丽隐杆线虫和果蝇中DCC与netrin同源物之间相互作用的遗传学证据。
