Journal
MOLECULAR AND CELLULAR NEUROSCIENCE
Volume 40, Issue 1, Pages 27-38Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mcn.2008.08.009
Keywords
Calcium; Ryanodine receptors; Axon growth inhibition; Growth cone collapse; Semaphorin 3A; Large vacuole; Macropinocytosis; Retrograde membrane trafficking; Actin filament
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Funding
- MEXT
- Grants-in-Aid for Scientific Research [21590196] Funding Source: KAKEN
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Growth cone collapse occurs in repulsive axon guidance and is accompanied by a reduction in the surface area of the plasma membrane of growth cones. However, the mechanism of this reduction is unclear. Here, we show that during growth cone collapse, caffeine-induced Ca2+ release from ryanodine-sensitive Ca2+ Stores triggers the formation of large vacuoles in growth cones by macropinocytosis, a clathrin-independent endocytosis for the massive retrieval of the cellular plasma membrane, and Subsequent retrograde membrane transport. We observed a significant correlation of the area of caffeine-induced macropinosomes with growth cone collapse. We also detected macropinocytosis induced by semaphorin 3A, a typical repulsive cue, and correlation between the area of semaphorin 3A-induced macropinocytic vacuoles and growth cone collapse. Moreover, jasplakinolide, an inhibitor of F-actin depolymerization, blocked caffeine-induced macropinocytosis. We propose that the coordinated regulation of actin cytoskeletal reorganization and macropinocytosis-mediated retrograde membrane trafficking may contribute to Ca2+-induced axon growth inhibition. (C) 2008 Elsevier Inc. All rights reserved.
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