Affiliation:
1. Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven CT 06520
Abstract
The small G protein Rac regulates cytoskeletal protein dynamics in neuronal growth cones and has been implicated in axon growth, guidance, and branching. Intracellular Ca2+is another well known regulator of growth cone function; however, effects of Rac activity on intracellular Ca2+metabolism have not been well characterized. Here, we investigate how Rac1 activity affects release of Ca2+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 Ca2+release sites. Multimode fluorescent microscopy was used to correlate microtubule and ER behavior, and ratiometric imaging was used to assess intracellular Ca2+dynamics. We report that Rac1 activity both promotes Ca2+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 Ca2+by 1) enhancing microtubule assembly which in turn promotes spread of the ER-based Ca2+release machinery into the growth cone periphery, and 2) by increasing ROS production which facilitated inositol 1,4,5-trisphosphate-dependent Ca2+release. These results cast Rac1 as a key modulator of intracellular Ca2+function in the neuronal growth cone.
Publisher
American Society for Cell Biology (ASCB)
Subject
Cell Biology,Molecular Biology
Cited by
22 articles.
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