当前位置: X-MOL 学术Proc. Natl. Acad. Sci. U.S.A. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
The auxiliary glutamate receptor subunit dSol-1 promotes presynaptic neurotransmitter release and homeostatic potentiation [Neuroscience]
Proceedings of the National Academy of Sciences of the United States of America ( IF 11.1 ) Pub Date : 2020-10-13 , DOI: 10.1073/pnas.1915464117
Beril Kiragasi 1 , Pragya Goel 1 , Sarah Perry 1 , Yifu Han 1 , Xiling Li 1 , Dion Dickman 1
Affiliation  

Presynaptic glutamate receptors (GluRs) modulate neurotransmitter release and are physiological targets for regulation during various forms of plasticity. Although much is known about the auxiliary subunits associated with postsynaptic GluRs, far less is understood about presynaptic auxiliary GluR subunits and their functions. At the Drosophila neuromuscular junction, a presynaptic GluR, DKaiR1D, localizes near active zones and operates as an autoreceptor to tune baseline transmission and enhance presynaptic neurotransmitter release in response to diminished postsynaptic GluR functionality, a process referred to as presynaptic homeostatic potentiation (PHP). Here, we identify an auxiliary subunit that collaborates with DKaiR1D to promote these synaptic functions. This subunit, dSol-1, is the homolog of the Caenorhabditis elegans CUB (Complement C1r/C1s, Uegf, Bmp1) domain protein Sol-1. We find that dSol-1 functions in neurons to facilitate baseline neurotransmission and to enable PHP expression, properties shared with DKaiR1D. Intriguingly, presynaptic overexpression of dSol-1 is sufficient to enhance neurotransmitter release through a DKaiR1D-dependent mechanism. Furthermore, dSol-1 is necessary to rapidly increase the abundance of DKaiR1D receptors near active zones during homeostatic signaling. Together with recent work showing the CUB domain protein Neto2 is necessary for the homeostatic modulation of postsynaptic GluRs in mammals, our data demonstrate that dSol-1 is required for the homeostatic regulation of presynaptic GluRs. Thus, we propose that CUB domain proteins are fundamental homeostatic modulators of GluRs on both sides of the synapse.



中文翻译:

辅助谷氨酸受体亚基dSol-1促进突触前神经递质的释放和体内稳态的增强[神经科学]

突触前谷氨酸受体(GluRs)调节神经递质的释放,并且是在各种形式的可塑性期间进行调节的生理学靶标。尽管对与突触后GluR相关的辅助亚基的了解很多,但对突触前辅助GluR亚基及其功能的了解却很少。在果蝇神经肌肉接头处,突触前GluR DKaiR1D,定位在活动区域​​附近,并作为自动受体来调节基线传递并增强突触前神经递质的释放,以响应突触后GluR功能的降低,这一过程称为突触前稳态增强(PHP)。在这里,我们确定了与DKaiR1D协作以促进这些突触功能的辅助亚基。此亚基dSol-1是秀丽隐杆线虫CUB(补体C1r / C1s,Uegf,Bmp1)域蛋白Sol-1的同源物。我们发现dSol-1在神经元中发挥功能,以促进基线神经传递并启用PHP表达(与DKaiR1D共享的属性)。有趣的是,dSol-1突触前过表达通过依赖DKaiR1D的机制足以增强神经递质的释放。此外,dSol-1对于在稳态信号传递过程中迅速增加活性区附近的DKaiR1D受体的丰度是必需的。连同最近的工作表明CUB域蛋白Neto2对于哺乳动物中突触后GluR的稳态调节是必要的,我们的数据表明dSol-1是突触前GluRs稳态调节所必需的。因此,我们建议CUB域蛋白是突触两侧GluRs的基本稳态调节剂。

更新日期:2020-10-13
down
wechat
bug