RRC ID 56247
Author Zhang S, Fan Z, Qiao P, Zhao Y, Wang Y, Jiang D, Wang X, Zhu X, Zhang Y, Huang B, Lu J, Li X.
Title miR-51 regulates GABAergic synapses by targeting Rab GEF GLO-4 and lysosomal trafficking-related GLO/AP-3 pathway in Caenorhabditis elegans.
Journal Dev. Biol.
Abstract A deficit of GABA (γ-aminobutyric acid) transmission will lead to epilepsy and other cognitive disorders. Recent evidence has shown that neuronal miRNAs affect various synapses, including GABAergic synapses. However, the miRNAs that control GABAergic synapses remain not fully understood. Here, we identified miR-51, a member of Caenorhabditis elegans miR-99/100 family, as a key regulator of GABAergic synapses. Loss of mir-51 increased PTZ (Pentylenetetrazole) and aldicarb hypersensitivities, and decreased the number of GABAergic synapses and abundance of GABAA receptors. A Rab guaninenucleotide exchange factor (GEF) GLO-4, a well-known component in lysosomal trafficking-related GLO-4/GLO-1/AP-3 (GLO/AP-3) pathway, was discovered to be the direct target of miR-51. Rescue experiments showed that GLO-4 expressed in GABAergic motor neurons functioned as a suppressor of miR-51. Disruption of glo-1 or AP-3 gene apm-3 attenuated the defects of GABAergic synapse in mir-51 mutants, suggesting miR-51 regulated GABAergic synapses through GLO/AP-3 pathway. The present study implies the essential roles of miRNAs on the nervous pathologies characterized by mis-regulated GABA signaling, such as epilepsy.
Volume 436(1)
Pages 66-74
Published 2018-4-1
DOI 10.1016/j.ydbio.2018.02.009
PII S0012-1606(17)30509-2
PMID 29476722
MeSH Adaptor Protein Complex 3 / metabolism Animals Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / metabolism* Cell Culture Techniques GABAergic Neurons / metabolism* GABAergic Neurons / physiology Guanine Nucleotide Exchange Factors / metabolism* Lysosomes / metabolism Lysosomes / physiology MicroRNAs / metabolism* Protein Transport / genetics* Protein Transport / physiology Signal Transduction / genetics Synapses / metabolism Synaptic Transmission / physiology
IF 2.936
C.elegans tm920