Local calcium changes regulate the length of growth cone filopodia

• Published in: Journal of neurobiology 2002-03, Vol.50 (4), p.263-275
• Main Authors: Cheng, Su, Geddis, Matthew S., Rehder, Vincent
• Format: Article
• Language: English
• Subjects: Animals; calcineurin; calcium; Calcium - metabolism; calcium green; Calcium Signaling - drug effects; Calcium Signaling - physiology; Calcium-Binding Proteins - antagonists & inhibitors; Calcium-Binding Proteins - metabolism; calmodulin; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell Movement - drug effects; Cell Movement - physiology; Cells, Cultured; Central Nervous System - cytology; Central Nervous System - embryology; Central Nervous System - metabolism; Chemotaxis - physiology; filopodia; Growth Cones - drug effects; Growth Cones - metabolism; Growth Cones - ultrastructure; NP–EGTA; Photolysis - drug effects; Pseudopodia - drug effects; Pseudopodia - metabolism; Pseudopodia - ultrastructure; Snails
• ISSN: 0022-3034; 1097-4695
• DOI: 10.1002/neu.10027

Previous studies have demonstrated that the free intracellular calcium concentration ([Ca2+]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 [Ca2+]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 [Ca2+]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 [Ca2+]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 Ca2+‐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 [Ca2+]i, but induced filopodial elongation on the entire growth cone. Elevation of [Ca2+]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 [Ca2+]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. © 2002 Wiley Periodicals, Inc. J Neurobiol 50: 263–275, 2002; DOI 10.1002/neu.10027