miR-51 regulates GABAergic synapses by targeting Rab GEF GLO-4 and lysosomal trafficking-related GLO/AP-3 pathway in Caenorhabditis elegans.
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.
['Zhang|Shuai|S|', 'Fan|Zhibin|Z|', 'Qiao|Ping|P|', 'Zhao|Yinsuo|Y|', 'Wang|Yanan|Y|', 'Jiang|Da|D|', 'Wang|Xiangming|X|', 'Zhu|Xiaojuan|X|', 'Zhang|Yu|Y|', 'Huang|Baiqu|B|', 'Lu|Jun|J|', 'Li|Xiaoxue|X|']
D033963:Adaptor Protein Complex 3 D000818:Animals D017173:Caenorhabditis elegans D029742:Caenorhabditis elegans Proteins D018929:Cell Culture Techniques D059330:GABAergic Neurons D020662:Guanine Nucleotide Exchange Factors D008247:Lysosomes D035683:MicroRNAs D021381:Protein Transport D015398:Signal Transduction D013569:Synapses D009435:Synaptic Transmission
miR-51 GABAergic synapses GLO-4 GLO/AP-3 pathway