| 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:
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PMID: 19570918 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
Authors:
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Xiao-Feng Zhang; Paul Forscher |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-07-01 |
Journal Detail:
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Title: Molecular biology of the cell Volume: 20 ISSN: 1939-4586 ISO Abbreviation: Mol. Biol. Cell Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2009-08-17 Completed Date: 2009-12-15 Revised Date: 2010-09-27 |
Medline Journal Info:
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Nlm Unique ID: 9201390 Medline TA: Mol Biol Cell Country: United States |
Other Details:
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Languages: eng Pagination: 3700-12 Citation Subset: IM |
Affiliation:
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Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven CT 06520, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals 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 | |
ID/Acronym/Agency:
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R01-NS051786/NS/NINDS NIH HHS; R01-NS28695/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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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 3.6.5.2/rac1 GTP-Binding Protein |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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