Follistatin-like 1 suppresses sensory afferent transmission by activating Na+,K+-ATPase

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...

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Main Authors: Li, Kai-Cheng (Author) , Zhang, Fang-Xiong (Author) , Li, Chang-Lin (Author) , Wang, Feng (Author) , Yu, Ming-Yan (Author) , Zhong, Yan-Qing (Author) , Zhang, Kai-Hua (Author) , Lu, Ying-Jin (Author) , Wang, Qiong (Author) , Ma, Xiao-Li (Author) , Yao, Jun-Ru (Author) , Wang, Jin-Yuan (Author) , Lin, Li-Bo (Author) , Han, Mei (Author) , Zhang, Yu-Qiu (Author) , Kuner, Rohini (Author) , Xiao, Hua-Sheng (Author) , Bao, Lan (Author) , Gao, Xiang (Author) , Zhang, Xu (Author)
Format: Article (Journal)
Language:English
Published: March 10, 2011
In: Neuron
Year: 2011, Volume: 69, Issue: 5, Pages: 974-987
ISSN:1097-4199
DOI:10.1016/j.neuron.2011.01.022
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.neuron.2011.01.022
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0896627311000705
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Author Notes:Kai-Cheng Li, Fang-Xiong Zhang, Chang-Lin Li, Feng Wang, Ming-Yan Yu, Yan-Qing Zhong, Kai-Hua Zhang, Ying-Jin Lu, Qiong Wang, Xiao-Li Ma, Jun-Ru Yao, Jin-Yuan Wang, Li-Bo Lin, Mei Han, Yu-Qiu Zhang, Rohini Kuner, Hua-Sheng Xiao, Lan Bao, Xiang Gao, and Xu Zhang

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520 |a 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. 
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