Follistatin-like 1 Suppresses Sensory Afferent Transmission by Activating Na+,K+-ATPase
Follistatin-like 1 Suppresses Sensory Afferent Transmission by Activating Na+,K+-ATPase
复制标题
卵泡抑素样 1 通过激活 Na ,K -ATP 酶抑制感觉传入传递
DOI：
10.1016/j.neuron.2011.01.022
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发表时间：
2011-03-10
期刊：
影响因子：
16.2
通讯作者：
Zhang, Xu
中科院分区：
文献类型：
--
作者：
Li, Kai-Cheng;Zhang, Fang-Xiong;Zhang, Xu
兴奋性突触传递受抑制性神经递质和神经调节剂的调节。我们发现，突触前分泌的卵泡抑素样蛋白(FSTL1)可以快速调节躯体感觉传入的突触传递，FSTL1是Na+，K+-ATPase(NKA)的直接激活剂。FSTL1蛋白在背根神经节(DRG)的小直径神经元中高表达。它通过小的半透明小泡运输到轴突终末，并以自发和去极化诱导的方式分泌。生化分析表明，FSTL1与NKA的α1亚基结合，使NKA活性升高。细胞外FSTL1通过激活NKA诱导培养细胞膜超极化，抑制脊髓脑片的传入突触传递。小鼠背根神经节小神经元FSTL1基因缺失导致突触传递增强，感觉超敏反应增强，鞘内注射FSTL1蛋白可降低这一效应。因此，依赖于FSTL1的NKA激活调节了躯体感觉的阈值。
Excitatory synaptic transmission is modulated by inhibitory neurotransmitters and neuromodulators. We found that the synaptic transmission of somatic sensory afferents can be rapidly regulated by a presynaptically secreted protein, follistatin-like 1 (FSTL1), which serves as a direct activator of Na+,K+-ATPase (NKA). The FSTL1 protein is highly expressed in small-diameter neurons of the dorsal root ganglion (DRG). It is transported to axon terminals via small translucent vesicles and secreted in both spontaneous and depolarization-induced manners. Biochemical assays showed that FSTL1 binds to the alpha 1 subunit of NKA and elevates NKA activity. Extracellular FSTL1 induced membrane hyperpolarization in cultured cells and inhibited afferent synaptic transmission in spinal cord slices by activating NKA. Genetic deletion of FSTL1 in small DRG neurons of mice resulted in enhanced afferent synaptic transmission and sensory hypersensitivity, which could be reduced by intrathecally applied FSTL1 protein. Thus, FSTL1-dependent activation of NKA regulates the threshold of somatic sensation.