卵泡抑素样蛋白 1 通过激活 Na+,K+-ATP 酶来抑制感觉传入的传递。
Follistatin-like 1 suppresses sensory afferent transmission by activating Na+,K+-ATPase.
机构信息
Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
出版信息
Neuron. 2011 Mar 10;69(5):974-87. doi: 10.1016/j.neuron.2011.01.022.
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 α1 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.
兴奋性突触传递受抑制性神经递质和神经调质的调节。我们发现躯体感觉传入的突触传递可以被一种突触前分泌的蛋白快速调节，这种蛋白叫做卵泡抑素样蛋白 1（Follistatin-like 1，FSTL1），它可以直接激活 Na(+)，K(+) - 三磷酸腺苷酶（Na(+)，K(+) - ATPase，NKA）。FSTL1 蛋白在背根神经节（dorsal root ganglion，DRG）的小直径神经元中高度表达。它通过小的半透明囊泡被运输到轴突末梢，并以自发和去极化诱导的方式分泌。生化测定表明 FSTL1 与 NKA 的α1 亚基结合并提高 NKA 活性。细胞外 FSTL1 通过激活 NKA 在培养细胞中诱导膜超极化，并在脊髓切片中抑制传入突触传递。在小鼠的小 DRG 神经元中，FSTL1 的遗传缺失导致传入突触传递增强和感觉过敏，鞘内应用 FSTL1 蛋白可以减少这种过敏。因此，FSTL1 依赖的 NKA 激活调节躯体感觉的阈值。
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