Function coupling of otoferlin with GAD65 acts to modulate GABAergic activity
作者机构:Department of Biomedical and Molecular SciencesQueen’s UniversityKingstonOntario K7L 3N6Canada Department of Anesthesiology&Perioperative CareUniversity of California IrvineIrvineCAUSA
出 版 物:《分子细胞生物学报:英文版》 (Journal of Molecular Cell Biology)
年 卷 期:2015年第7卷第2期
页 面:168-179页
核心收录:
主 题:otoferlin GAD65 GABA neurotransmitter exocytosis
摘 要:Otoferlin,an integral membrane protein implicated in a late stage of exocytosis,has been reported to play a critical role in hearing although the underlying mechanisms remain ***,its widespread tissue distribution infers a more ubiquitous role in synaptic vesicle ***,an excitatory neurotransmitter,is converted to its inhibitory counterpart,g-aminobutyric acid(GABA),by L-glutamic acid decarboxylase(GAD),which exists in soluble(GAD67)and membrane-bound(GAD65)*** the first time,we have revealed a close association between otoferlin and GAD65 in both HEK293 and neuronal cells,including SHSY5Y neuroblastoma and primary rat hippocampus cells,showing a direct interaction between GAD65 and otoferlin’s C2 *** primary rat hippocampus cells,otoferlin and GAD65 co-localized in a punctate pattern within the cell body,as well as in the axon along the path of vesicular ***,GABA is virtually abolished in otoferlin-knockdown neuronal cells whereas otoferlin overexpression markedly increases endogenous *** attenuation in otoferlin-knockdown primary cells is correlated with diminished L-type calcium *** previously unknown and close correlation demonstrates that otoferlin,through GAD65,modulates GABAergic *** discovery of otoferlin–GAD65 functional coupling provides a newavenue for understanding the molecular mechanism by which otoferlin functions in neurological pathways.