ASYMMETRIC RETRACTION OF GROWTH CONE FILOPODIA FOLLOWING FOCAL INACTIVATION OF CALCINEURIN

THE neuronal growth cone is thought to be the site of decision making in nerve growth and guidance(1,2). One likely mechanism of how the gro wth cone translates various extracellular cues into directed motility involves rises in intracellular calcium, A variety of physiological cu es, such as adhesion molecules and neurotransmitters, increases intrac ellular calcium(1), and artificial manipulations of growth cone calciu m levels affect growth cone morphology and neurite outgrowth(3). The m olecular events downstream of calcium fluxes are incompletely understo od, Here we show that calcineurin, a protein phosphatase enriched in g rowth cones that is dependent on calcium ions and calmodulin(4), funct ions in neurite outgrowth and directed filopodial motility in cultured chick dorsal root ganglia neurons. Cyclosporin A and FK506, inhibitor s of calcineurin(5), delayed neuritogenesis and inhibited neurite exte nsion, Chromophore-assisted laser inactivation of calcineurin io regio ns of growth cones causes localized filopodial and lamellipodial retra ction and influences the direction of subsequent outgrowth. We suggest that a spatial distribution of calcineurin activity within the growth cone can regulate motility and direct outgrowth.