3月10日,，美國《神經(jīng)元》（Neuron ）雜志發(fā)表了中科院上海生科院神經(jīng)所張旭研究員的博士后李開誠、研究生張方雄,、李昌林和王烽等共同完成的研究論文,，發(fā)現(xiàn)了傳導(dǎo)痛覺的背根節(jié)神經(jīng)元可以釋放一種名為濾泡素抑制素樣蛋白1（follistatin-like 1, FSTL1）的蛋白質(zhì)，通過激動初級感覺傳入神經(jīng)纖維上的鈉-鉀泵，調(diào)節(jié)痛覺等感覺信息的傳遞,。
神經(jīng)元消耗能量,，通過鈉-鉀泵（Na+, K+-ATPase），在細胞漿中濃集鉀離子并排出細胞內(nèi)的鈉離子,，從而維持細胞膜內(nèi)外的鈉,、鉀離子濃度梯度,，調(diào)控細胞膜電位和興奮性,，對調(diào)節(jié)神經(jīng)元功能起十分重要的作用。然而,，人們一直不清楚除了ATP,、鈉和鉀離子對鈉-鉀泵的驅(qū)動作用，以及一些神經(jīng)遞質(zhì),、激素通過它們的受體間接地調(diào)節(jié)鈉-鉀泵活性以外,，身體內(nèi)是否存在可以直接激動鈉-鉀漿的物質(zhì)，并對神經(jīng)系統(tǒng)功能進行調(diào)節(jié),。
作者通過一系列的實驗發(fā)現(xiàn)，傳導(dǎo)痛覺的背根節(jié)神經(jīng)元高表達FSTL1,，并且通過清亮小泡將FSTL1運輸至脊髓內(nèi)的傳入神經(jīng)終末釋放,，直接與位于感覺傳入神經(jīng)終末突觸前膜上的鈉-鉀泵α1亞基相結(jié)合,，增強鈉-鉀泵活性,，使細胞膜超級化，從而對感覺傳入神經(jīng)終末的興奮性突觸傳遞起抑制性調(diào)控作用,。課題組與南京大學(xué)模式動物研究所高翔教授的科研團隊密切合作,，制備了當時國內(nèi)第一例條件式敲除小鼠,，在背根節(jié)神經(jīng)元中特異性敲除了FSTL1的基因,。研究發(fā)現(xiàn)FSTL1條件式敲除小鼠興奮性突觸傳遞增強,，痛覺敏感度增強。因此,，F(xiàn)STL1作為第一個被發(fā)現(xiàn)的內(nèi)源性鈉-鉀泵激動劑,，對于保持正常的軀體感覺是必需的,，F(xiàn)STL1減少則會導(dǎo)致異常痛覺。該發(fā)現(xiàn)表明內(nèi)源性鈉-鉀泵激動劑可以通過調(diào)控突觸傳遞對神經(jīng)系統(tǒng)功能起重要的影響,。
該研究到了中國科學(xué)院、科技部973項目,、國家自然科學(xué)基金等項目的資助,。
FSTL1-鈉鉀泵系統(tǒng)調(diào)節(jié)突觸傳遞的模式圖：膜去極化導(dǎo)致突觸囊泡和FSTL1囊泡釋放,，釋放的FSTL1激活位于初級感覺傳入神經(jīng)終末突觸前膜上的鈉鉀泵的a1亞基，使細胞膜超級化,，從而對初級感覺傳入神經(jīng)終末的興奮性突觸傳遞起抑制性調(diào)控作用,。（生物谷Bioon.com）
生物谷推薦原始出處：
Neuron doi:10.1016/j.neuron.2011.01.022
Follistatin-like 1 Suppresses Sensory Afferent Transmission by Activating Na+,K+-ATPase
Kai-Cheng Li1, 7, Fang-Xiong Zhang1, 2, 7, Chang-Lin Li1, 7, Feng Wang1, 7, Ming-Yan Yu2, Yan-Qing Zhong3, Kai-Hua Zhang1, Ying-Jin Lu1, Qiong Wang3, Xiao-Li Ma1, Jun-Ru Yao1, Jin-Yuan Wang1, Li-Bo Lin4, Mei Han6, Yu-Qiu Zhang6, Rohini Kuner5, Hua-Sheng Xiao4, Lan Bao3, Xiang Gao2, , and Xu Zhang1,
Highlights
FSTL1 is expressed in DRG and secreted via small vesicles at afferent terminals
FSTL1 binds to the α1 subunit of Na+,K+-ATPase and elevates its activity
FSTL1 suppresses the synaptic transmission by activating Na+,K+-ATPase
FSTL1 is required for maintaining the normal threshold of somatic sensation
Summary
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.
