Sci. STKE, 13 March 2001
Neurobiology Switching Sides to Get Ahead
As the nervous system of the developing vertebrate embryo is laid down, the guidance molecule netrin attracts the growth cones of advancing axons to the embryo's midline. However, as soon as the growth cones cross the midline, they switch allegiance, ignoring netrin and instead responding to Slit, which repels the growth cones away from the midline. Two papers tackle how growth cones make their way through competing signals. Stein and Tessier-Lavigne show that this switch is the result of the cytoplasmic domain of the Slit receptor, Robo, binding to the cytoplasmic domain of the netrin receptor DCC. Thus, the dwindling effects of netrin on growth cones are directly linked to their increasing responsiveness to the repellent effects of Slit. This interlocked silencing mechanism prevents the growth cone from being trapped in a tug-of-war between the attractive and repellent activities of two opposing guidance molecules. Stein et al. address the mechanism by which netrin exerts its effects. In contrast to a recent suggestion that netrin acts through the adenosine A2B receptor, the authors show that netrin binds directly to the DCC protein and that A2B activation is not required for netrin's effects on axon outgrowth or neuron attraction. Thus, DCC is the primary receptor responsible for netrin's actions. Dickson provides a Perspective on axon guidance.
E. Stein, M. Tessier-Lavigne, Hierarchical organization of guidance receptors: Silencing of netrin attraction by Slit through a Robo/DCC receptor complex. Science 291, 1928-1938 (2001). [Abstract] [Full Text]
E. Stein, Y. Zou, M.-m. Poo, M. Tessier-Lavigne, Binding of DCC by netrin-1 to mediate axon guidance independent of adenosine A2B receptor activation. Science 291, 1976-1982 (2001). [Abstract] [Full Text]
B. J. Dickson, Moving on. Science 291, 1910-1911 (2001). [Full Text]
Citation: Switching Sides to Get Ahead. Sci. STKE 2001, tw4 (2001).
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