Abbreviated Journal Title
Proc. Natl. Acad. Sci. U. S. A.
Keywords
Bcl-2; synaptic transmission; mitochondria; cell death; ABT-737; MITOCHONDRIAL FISSION; CELL-DEATH; EMBRYONIC NEURONS; AXONAL-TRANSPORT; APOPTOSIS; RELEASE; DYNAMICS; FUSION; BAX; TRANSMISSION; Multidisciplinary Sciences
Abstract
Maturation of neuronal synapses is thought to involve mitochondria. Bcl-X-L protein inhibits mitochondria-mediated apoptosis but may have other functions in healthy adult neurons in which Bcl-X-L is abundant. Here, we report that overexpression of Bcl-X-L postsynaptically increases frequency and amplitude of spontaneous miniature synaptic currents in rat hippocampal neurons in culture. Bcl-X-L, overexpressed either pre or postsynaptically, increases synapse number, the number and size of synaptic vesicle clusters, and mitochondrial localization to vesicle clusters and synapses, likely accounting for the changes in miniature synaptic currents. Conversely, knockdown of Bcl-X-L or inhibiting. it with ABT-737 decreases these morphological parameters. The mitochondrial fission protein, dynamin-related protein 1 (Drp1), is a GTPase known to localize to synapses and affect synaptic function and structure. The effects of Bcl-X-L appear mediated through Drp1 because overexpression of Drp1 increases synaptic markers, and overexpression of the dominant-negative dnDrp1-K38A decreases them. Furthermore, Bcl-X-L coimmunoprecipitates with Drp1 in tissue lysates, and in a recombinant system, Bcl-X-L protein stimulates GTPase activity of Drp1. These findings suggest that Bcl-X-L positively regulates Drp1 to alter mitochondrial function in a manner that stimulates synapse formation.
Journal Title
Proceedings of the National Academy of Sciences of the United States of America
Volume
105
Issue/Number
6
Publication Date
1-1-2008
Document Type
Article
Language
English
First Page
2169
Last Page
2174
WOS Identifier
ISSN
0027-8424
Recommended Citation
Li, Hongwei; Chen, Yingbei; Jones, Adrienne F.; Sanger, Richard H.; Collis, Leon P.; Flannery, Richard; McNay, Ewan C.; Yu, Tingxi; Schwarzenbacher, Robert; Bossy, Bliase; Bossy-Wetzel, Ella; Bennett, Michael V. L.; Pypaert, Marc; Hickman, John A.; Smith, Peter J. S.; Hardwick, Marie; and Jones, Elizabeth A., "Bcl-X-L induces Drp1-dependent synapse formation in cultured hippocampal neurons" (2008). Faculty Bibliography 2000s. 605.
https://stars.library.ucf.edu/facultybib2000/605
Comments
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