Document Detail

Rac1 modulates stimulus-evoked Ca(2+) release in neuronal growth cones via parallel effects on microtubule/endoplasmic reticulum dynamics and reactive oxygen species production.
MedLine Citation:
PMID:  19570918     Owner:  NLM     Status:  MEDLINE    
The small G protein Rac regulates cytoskeletal protein dynamics in neuronal growth cones and has been implicated in axon growth, guidance, and branching. Intracellular Ca(2+) is another well known regulator of growth cone function; however, effects of Rac activity on intracellular Ca(2+) metabolism have not been well characterized. Here, we investigate how Rac1 activity affects release of Ca(2+) from intracellular endoplasmic reticulum (ER) stores stimulated by application of serotonin (5-hydroxytriptamine). We also address how Rac1 effects on microtubule assembly dynamics affect distribution of Ca(2+) release sites. Multimode fluorescent microscopy was used to correlate microtubule and ER behavior, and ratiometric imaging was used to assess intracellular Ca(2+) dynamics. We report that Rac1 activity both promotes Ca(2+) release and affects its spatial distribution in neuronal growth cones. The underlying mechanism involves synergistic Rac1 effects on microtubule assembly and reactive oxygen species (ROS) production. Rac1 activity modulates Ca(2+) by 1) enhancing microtubule assembly which in turn promotes spread of the ER-based Ca(2+) release machinery into the growth cone periphery, and 2) by increasing ROS production which facilitated inositol 1,4,5-trisphosphate-dependent Ca(2+) release. These results cast Rac1 as a key modulator of intracellular Ca(2+) function in the neuronal growth cone.
Xiao-Feng Zhang; Paul Forscher
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-07-01
Journal Detail:
Title:  Molecular biology of the cell     Volume:  20     ISSN:  1939-4586     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-08-17     Completed Date:  2009-12-15     Revised Date:  2010-09-27    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3700-12     Citation Subset:  IM    
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven CT 06520, USA.
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MeSH Terms
Aplysia / cytology,  metabolism
Calcium / metabolism*
Cells, Cultured
Endoplasmic Reticulum / metabolism*
Growth Cones / metabolism*,  ultrastructure
Inositol 1,4,5-Trisphosphate / metabolism
Microscopy, Fluorescence
Microtubules / metabolism*,  ultrastructure
Neurons* / cytology,  metabolism
Reactive Oxygen Species / metabolism*
Serotonin / metabolism
Signal Transduction / physiology
Type C Phospholipases / metabolism
rac1 GTP-Binding Protein / metabolism*
Grant Support
Reg. No./Substance:
0/Reactive Oxygen Species; 50-67-9/Serotonin; 7440-70-2/Calcium; 85166-31-0/Inositol 1,4,5-Trisphosphate; EC 3.1.4.-/Type C Phospholipases; EC GTP-Binding Protein

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