Yu Timothy W, Hao Joe C, Lim Wendell, Tessier-Lavigne Marc, Bargmann Cornelia I
Howard Hughes Medical Institute, Program in Neuroscience, Department of Anatomy and of Biochemistry and Biophysics, The University of California, San Francisco, California 94143, USA.
Nat Neurosci. 2002 Nov;5(11):1147-54. doi: 10.1038/nn956.
The C. elegans SAX-3/Robo receptor acts in anterior-posterior, dorsal-ventral and midline guidance decisions. Here we show that SAX-3 signaling involves the C. elegans Enabled protein UNC-34 and an unexpected Netrin-independent function of the Netrin receptor UNC-40/DCC. Genetic interactions with gain- and loss-of-function mutations suggest that unc-34 and unc-40 act together with sax-3 in several guidance decisions, but the C. elegans Netrin gene unc-6 does not act in the same genetic pathways. Within the migrating axon, sax-3, unc-34 and unc-40 all act cell-autonomously. Our results support a role for UNC-34/Enabled proteins in SAX-3-mediated repulsion, and show that UNC-40/DCC can potentiate SAX-3/Robo signaling via a mechanism that may involve direct binding of the two guidance receptors. A combinatorial logic dictates alternative functions for UNC-40/DCC, which can act in attraction to UNC-6/Netrin, repulsion from Netrin (with UNC-5), or repulsion from Slit (with SAX-3).
秀丽隐杆线虫的SAX-3/Robo受体在前后、背腹和中线导向决策中发挥作用。我们在此表明，SAX-3信号传导涉及秀丽隐杆线虫的Enabled蛋白UNC-34以及Netrin受体UNC-40/DCC一个意想不到的不依赖Netrin的功能。与功能获得和功能缺失突变的遗传相互作用表明，unc-34和unc-40在几个导向决策中与sax-3共同起作用，但秀丽隐杆线虫的Netrin基因unc-6不在相同的遗传途径中起作用。在迁移的轴突内，sax-3、unc-34和unc-40均以细胞自主方式起作用。我们的结果支持UNC-34/Enabled蛋白在SAX-3介导的排斥中发挥作用，并表明UNC-40/DCC可通过一种可能涉及两种导向受体直接结合的机制增强SAX-3/Robo信号传导。一种组合逻辑决定了UNC-40/DCC的多种功能，它可以在对UNC-6/Netrin的吸引、对Netrin的排斥（与UNC-5一起）或对Slit的排斥（与SAX-3一起）中起作用。
