Ca2+-Dependent Regulation of Rho GTPases Triggers Turning of Nerve Growth Cones

Cytoplasmic Ca2+ elevation and changes in Rho GTPase activity are both known to mediate axon guidance by extracellular factors, but the causal relationship between these two events has been unclear. Here we show that direct elevation of cytoplasmic Ca2+ by extracellular application of a low concentr...

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Bibliographic Details
Published in:The Journal of neuroscience 2005-03, Vol.25 (9), p.2338-2347
Main Authors: Jin, Ming, Guan, Chen-bing, Jiang, Yun-ai, Chen, Gang, Zhao, Chun-tao, Cui, Kai, Song, Yuan-quan, Wu, Chien-ping, Poo, Mu-ming, Yuan, Xiao-bing
Format: Article
Language:English
Subjects:
Animals
Bacterial Proteins - pharmacology
Bacterial Toxins - pharmacology
Blotting, Western - methods
Brain-Derived Neurotrophic Factor - pharmacology
Calcium - metabolism
cdc42 GTP-Binding Protein - pharmacology
Cell Line
Chelating Agents - pharmacology
Development/Plasticity/Repair
Diagnostic Imaging - methods
Dose-Response Relationship, Drug
Drug Interactions
Egtazic Acid - analogs & derivatives
Egtazic Acid - pharmacology
Embryo, Nonmammalian
Enzyme Activation - drug effects
Enzyme Inhibitors - pharmacology
Green Fluorescent Proteins - pharmacology
Growth Cones - drug effects
Growth Cones - physiology
Humans
Nerve Growth Factors - pharmacology
Netrin-1
Neurons - cytology
Neurons - physiology
rho GTP-Binding Proteins - metabolism
Ryanodine - pharmacology
Spinal Cord - cytology
Thapsigargin - pharmacology
Time Factors
Transfection - methods
Tumor Suppressor Proteins - pharmacology
Xenopus
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Summary:Cytoplasmic Ca2+ elevation and changes in Rho GTPase activity are both known to mediate axon guidance by extracellular factors, but the causal relationship between these two events has been unclear. Here we show that direct elevation of cytoplasmic Ca2+ by extracellular application of a low concentration of ryanodine, which activated Ca2+ release from intracellular stores, upregulated Cdc42/Rac, but downregulated RhoA, in cultured cerebellar granule cells and human embryonic kidney 293T cells. Chemoattractive turning of the growth cone triggered by a gradient of ryanodine was blocked by overexpression of mutant forms of Cdc42 but not of RhoA in Xenopus spinal cord neurons. Furthermore, Ca2+-induced GTPase activity correlated with activation of protein kinase C and required a basal activity of Ca2+/calmodulin-dependent protein kinase II. Thus, Rho GTPases may mediate axon guidance by linking upstream Ca2+ signals triggered by guidance factors to downstream cytoskeletal rearrangements.
ISSN:0270-6474
1529-2401
1529-2401
DOI:10.1523/JNEUROSCI.4889-04.2005