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Synaptosomes secrete and uptake functionally active micro RNA s via exocytosis and endocytosis pathways
Author(s) -
Xu Jie,
Chen Qun,
Zen Ke,
Zhang Chenyu,
Zhang Qipeng
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12057
Subject(s) - rna , synaptosome , secretion , exocytosis , biology , endocytosis , microbiology and biotechnology , synaptic vesicle , messenger rna , biochemistry , cell , vesicle , gene , in vitro , membrane
In this study, we first characterized synaptosome micro RNA (mi RNA ) profiles using microarray and qRT ‐ PCR . Micro RNA s were detected in isolated synaptic vesicles, and Ago2 immunoprecipitation studies revealed an association between mi RNA s and Ago2. Second, we found that miR‐29a, miR‐99a, and miR‐125a were significantly elevated in synaptosome supernatants after depolarization. Mi RNA secretion by the synaptosome was Ca 2+ ‐dependent and was inhibited by the exocytosis inhibitor, okadaic acid. Furthermore, application of nerve growth factor increased mi RNA secretion without altering the spontaneous release of mi RNA s. Conversely, kainic acid decreased mi RNA secretion and enhanced the spontaneous release of mi RNA s. These results indicate that synaptosomes could secrete mi RNA s. Finally, synthesized mi RNA s were taken up by synaptosomes, and the endocytosis inhibitor Dynasore blocked this process. After incubation with miR‐125a, additional miR‐125a was bound to Ago2 in the synaptosome, and expression of the miR‐125a target gene ( PSD 95 mRNA ) was decreased; these findings suggest that the ingested mi RNA s were assembled in the RNA‐induced silencing complex, resulting in the degradation of target mRNA s. To our knowledge, this is the first study that demonstrates the secretion of mi RNA s by synaptosomes under physiological stimulation and demonstrates that secreted mi RNA s might be functionally active after being taken up by the synaptic fraction via the endocytic pathway.