Chapter 10 Contributions of multiple forms of myosin to nerve outgrowth

Bridgman, Paul C.; Rochlin, M. William; Lewis, A.K.; Evans, Leah

doi:10.1016/s0079-6123(08)61130-9

Cited by 8 publications

(10 citation statements)

References 31 publications

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“…Gelsolin, whose activity is calcium dependent, regulates actin polymerization by severing and capping of f-actin (Carlier, 1998;Sun et al, 1999). Myosins are regulated by Ca 2ϩ or Ca 2ϩ /calmodulin (Swanljung-Collins and Collins, 1991;Bahler et al, 1994), and influence the retrograde flow of actin that has been linked to both neurite outgrowth and filopodial behavior (Bridgman et al, 1994;Lin et al, 1996). It will be important in future studies to further investigate which signaling pathways orchestrate changes in filopodial behavior.…”

Section: A Global Increase In Calcium Causes Filopodia To Elongatementioning

confidence: 99%

Local calcium changes regulate the length of growth cone filopodia

2002

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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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Section: A Global Increase In Calcium Causes Filopodia To Elongatementioning

confidence: 99%

Local calcium changes regulate the length of growth cone filopodia

2002

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“…Neurite outgrowth is known to be influenced greatly by cytoplasmic free calcium levels ([Ca 2ϩ ]C) and energy availability. Calcium regulates cytoskeletal dynamics (microfilament and microtubule polymerization) and membrane trafficking (Mattson, 1992;De Camilli and Takei, 1996), while adenosine triphosphate (ATP) is required for running ''motor proteins'' and for phosphorylation reactions (Bridgman et al, 1994;Desai et al, 1997), critical for neurite outgrowth. Two major functions of mitochondria are to generate ATP and to regulate cellular calcium homeostasis (see McCormack and Denton, 1993;Simpson and Russell, 1998 for review).…”

Section: Introductionmentioning

confidence: 99%

Evidence for mitochondrial control of neuronal polarity

Mattson¹,

Partin²

1999

J. Neurosci. Res.

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An early and essential step in the formation of functional neuronal circuits is the establishment of cell polarity, a process involving the morphological and functional differentiation of the axon (axonogenesis). We now report that treatment of cultured embryonic hippocampal neurons with ethidium bromide (EtBr; an agent that depletes mitochondrial DNA), prior to the establishment of cell polarity, prevents axon formation while permitting outgrowth of minor processes. The polarity-suppressing action of EtBr occurs under conditions of maintained cellular ATP levels, and is not mimicked by ATP-depleting agents (iodoacetate, p-(trifluoromethyoxy)phenylhydrazone [FCCP], and cyanide). Levels of tau, a microtubule-associated protein involved in axonogenesis, were not decreased in neurons treated with EtBr. Electron and confocal microscope analyses showed that EtBr treatment altered mitochondrial ultrastructure and subcellular localization. Basal levels of intracellular calcium were elevated 2- to 3-fold, intramitochondrial calcium levels were greatly increased, and mitochondrial transmembrane potential was decreased in EtBr-treated neurons. Exposure of neurons to a calcium ionophore prevented axonogenesis. Confocal images of intracellular calcium levels and mitochondrial localization in the same cells revealed congregations of mitochondria at the base of the axon associated with local reductions of intracellular calcium levels. When taken together with previous data indicating important roles for calcium in regulating neurite outgrowth, the present findings suggest critical roles for mitochondrial function and modulation of calcium homeostasis in the establishment of neuronal polarity.

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“…Specifically, neuronal growth cones contain multiple isoforms of nonmuscle myosins I, 11, and probably V (Miller et al, 1992;Murakami and Elzinga, 1992;Bridgman et al, 1994;Rochlin et al, 1995).…”

Section: Introductionmentioning

confidence: 99%