Local calcium changes regulate the length of growth cone filopodia |
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Authors: | Cheng Su Geddis Matthew S Rehder Vincent |
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Institution: | Biology Department, Georgia State University, University Plaza, 402 Kell Hall, Atlanta, Georgia 30303, USA. |
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Abstract: | Previous studies have demonstrated that the free intracellular calcium concentration (Ca(2+)](i)) in growth cones can act as an important regulator of growth cone behavior. Here we investigated whether there is a spatial and temporal correlation between Ca(2+)](i) and one particular aspect of growth cone behavior, namely the regulation of growth cone filopodia. Calcium was released from the caged compound NP-EGTA (o-nitrophenyl EGTA tetrapotassium salt) to simulate a signaling event in the form of a transient increase in Ca(2+)](i). In three different experimental paradigms, we released calcium either globally (within an entire growth cone), regionally (within a small area of the lamellipodium), or locally (within a single filopodium). We demonstrate that global photolysis of NP-EGTA in growth cones caused a transient increase in Ca(2+)](i) throughout the growth cone and elicited subsequent filopodial elongation that was restricted to the stimulated growth cone. Pharmacological blockage of either calmodulin or the Ca(2+)-dependent phosphatase, calcineurin, inhibited the effect of uncaging calcium, suggesting that these enzymes are acting downstream of calcium. Regional uncaging of calcium in the lamellipodium caused a regional increase in Ca(2+)](i), but induced filopodial elongation on the entire growth cone. Elevation of Ca(2+)](i) locally within an individual filopodium resulted in the elongation of only the stimulated filopodium. These findings suggest that the effect of an elevation of Ca(2+)](i) on filopodial behavior depends on the spatial distribution of the calcium signal. In particular, calcium signals within filopodia can cause filopodial length changes that are likely a first step towards directed filopodial steering events seen during pathfinding in vivo. |
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