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Sci. STKE, 9 July 2002
Vol. 2002, Issue 140, p. tw239
[DOI: 10.1126/stke.2002.140.tw239]


Growth Cones Do Redox Signals Cause Collapse?

Attractive and repulsive guidance cues direct neuronal growth cones as they explore their environment. Ligand-receptor interactions at the cell surface transduce signals to the growth cone cytoskeleton to facilitate such pathfinding. However, the molecular details of how this occurs have not been clear. For example, secreted and transmembrane forms of semaphorins elicit a repulsive response in growth cones through a receptor called plexin. Terman et al. report that plexin may modulate actin dynamics through its association with MICAL, a cytoplasmic oxidoreductase. In developing Drosophila, MICAL is expressed in the central nervous system and is present in neuronal cell bodies, axons, and growth cones. Loss-of-function MICAL mutant flies showed axon-guidance defects similar to those seen in semaphorin and plexin mutant flies. This defect was rescued upon expression of wild-type MICAL in the MICAL mutant embryos. The NH2-terminus of MICAL resembles a flavoprotein monooxygenase that catalyzes oxidation-reduction reactions. Expression of a protein harboring a mutation within this domain also caused similar axon-guidance defects. When cultured rat neurons, which also express MICAL, were treated with a monooxygenase inhibitor, growth cone repulsion normally induced by the presence of semaphorin was inhibited. These observations suggest that plexin may signal through MICAL, stimulating a redox signaling mechanism to regulate actin or proteins that modulate actin. Relevant MICAL substrates remain to be identified.

J. R. Terman, T. Mao, R. J. Pasterkamp, H.-H. Yu, A.L. Kolodkin, MICALs, a Family of Conserved Flavoprotein Oxidoreductases, Function in Plexin-Mediated Axonal Repulsion. Cell 109, 887-900 (2002). [Online Journal]

Citation: Do Redox Signals Cause Collapse? Sci. STKE 2002, tw239 (2002).

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