Stop on Green, Go on Red

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Science  22 Apr 2005:
Vol. 308, Issue 5721, pp. 468
DOI: 10.1126/science.308.5721.468a

Neuronal growth cones flaunt cell surface receptors that sense attractive and repulsive guidance cues as axons make their way to their destinations. Some of these cues are cell-surface proteins, too, and serve as receptor ligands. But what if both receptor and ligand are present in the same growth cone, as is the case with the Eph receptor tyrosine kinases and ephrins, their cognate, membrane-bound ligands?

Marquardt et al. propose that Eph receptors and ephrins segregate into subdomains of the growth cone membrane, allowing them to mediate repulsion and attraction independently. Motor neurons from the chick embryo spinal cord express the receptor EphA and the ligand ephrin-A. When neurons were treated with soluble EphA or ephrin-A, and then with antibodies that promoted clustering, the corresponding cell-surface receptors and ligands were observed to be partitioned into distinct membrane domains on the growth cone. Chimeric EphA and ephrin-A molecules were engineered to force a spatial intermingling of ligand and receptor, and expression of either chimera interfered with the growth cone response to soluble EphA or ephrin-A, indicating that spatial separation of endogenous receptors and ligands facilitates their responses to transcellular cues. The segregation of Eph and ephrin molecules in growth cones may enable axons to see both stop and go signals as they travel to their targets. — LDC

Cell 121, 127 (2005).

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