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Converting Repulsion to Attraction

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Science  14 Oct 2005:
Vol. 310, Issue 5746, pp. 199
DOI: 10.1126/science.310.5746.199c

Growth cones guide neurons to their targets by monitoring chemoattractive and chemorepellant cues. Many cues elicit localized increases in cytosolic free calcium concentration ([Ca2+]c) but, curiously, both attractive and repulsive diffusible cues can increase local [Ca2+] so that the growth cone turns toward (attraction) or away from (repulsion) the side with greater [Ca2+]c. Ooashi et al. used focal laser-induced photolysis of caged Ca2+ to transiently increase local [Ca2+]c in the growth cones of dorsal root ganglion neurons grown on different substrates. Neurons grown on L1 or N-cadherin substrates turned toward, whereas neurons grown on laminin turned away from, the side on which [Ca2+]c was greater. Neurons grown on L1 and N-cadherin substrates showed increased cyclic AMP (cAMP) binding to the regulatory subunits of cAMP-dependent protein kinase. Inhibition of cAMP signaling converted Ca2+-mediated attraction to repulsion, whereas pharmacological activation of protein kinase A converted Ca2+-mediated repulsion to attraction. Analysis of calcium signals and of the turning behavior of neurons from mice lacking the type 3 ryanodine receptor isoform (RyR3) implicated RyR3 in protein kinase A-dependent calcium-induced calcium release and attractive turning. The source of the cytosolic Ca2+ signal—rather than its amplitude—determined turning behavior. Thus, a Ca2+ signal that triggers calcium-induced calcium release from intracellular stores stimulates attractive turning, whereas a Ca2+ signal without calcium-induced calcium release elicits repulsion. — EMA

J. Cell Biol. 170, 1159 (2005).

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