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The Journal of Neuroscience, January 21, 2009, 29(3):638-652; doi:10.1523/JNEUROSCI.3845-08.2009

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Development/Plasticity/Repair
Protein Synthesis in Distal Axons Is Not Required for Growth Cone Responses to Guidance Cues

Florence K. Roche, Bonnie M. Marsick, and Paul C. Letourneau

Department of Neuroscience, Graduate Program in Neuroscience, University of Minneapolis, Minneapolis, Minnesota 55455

Correspondence should be addressed to Paul C. Letourneau, Department of Neuroscience, Graduate Program in Neuroscience, University of Minneapolis, 6-145 Jackson Hall, Minneapolis, MN 55455. Email: letou001{at}umn.edu

Recent evidence suggests that growth cone responses to guidance cues require local protein synthesis. Using chick neurons, we investigated whether protein synthesis is required for growth cones of several types to respond to guidance cues. First, we found that global inhibition of protein synthesis stops axonal elongation after 2 h. When protein synthesis inhibitors were added 15 min before adding guidance cues, we found no changes in the typical responses of retinal, sensory, and sympathetic growth cones. In the presence of cycloheximide or anisomycin, ephrin-A2, slit-3, and semaphorin3A still induced growth cone collapse and loss of actin filaments, nerve growth factor (NGF) and neurotrophin-3 still induced growth cone protrusion and increased filamentous actin, and sensory growth cones turned toward an NGF source. In compartmented chambers that separated perikarya from axons, axons grew for 24–48 h in the presence of cycloheximide and responded to negative and positive cues. Our results indicate that protein synthesis is not strictly required in the mechanisms for growth cone responses to many guidance cues. Differences between our results and other studies may exist because of different cellular metabolic levels in in vitro conditions and a difference in when axonal functions become dependent on local protein synthesis.

Key words: growth cone; guidance; protein synthesis; axon; actin; RhoA


Received Aug. 12, 2008; revised Nov. 4, 2008; accepted Dec. 2, 2008.

Correspondence should be addressed to Paul C. Letourneau, Department of Neuroscience, Graduate Program in Neuroscience, University of Minneapolis, 6-145 Jackson Hall, Minneapolis, MN 55455. Email: letou001{at}umn.edu




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