The Bi-Functional Paxilline Enriched in Skin Secretion of Tree Frogs (Hyla japonica) Targets the KCNK18 and BKCa Channels

被引:1
|
作者
Yin, Chuanling [1 ]
Zeng, Fanpeng [1 ]
Huang, Puyi [1 ]
Shi, Zhengqi [1 ]
Yang, Qianyi [1 ]
Pei, Zhenduo [1 ]
Wang, Xin [1 ]
Chai, Longhui [1 ]
Zhang, Shipei [1 ]
Yang, Shilong [1 ]
Dong, Wenqi [1 ]
Lu, Xiancui [1 ]
Wang, Yunfei [1 ]
机构
[1] Northeast Forestry Univ, Coll Wildlife & Protected Area, Harbin 150040, Peoples R China
基金
中国国家自然科学基金;
关键词
tree frogs; skin secretion; paxilline; KCNK18; defensive strategy; POISON FROGS; AMPHIBIAN SKIN; ALKALOIDS; PEPTIDE; PREY;
D O I
10.3390/toxins15010070
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
The skin secretion of tree frogs contains a vast array of bioactive chemicals for repelling predators, but their structural and functional diversity is not fully understood. Paxilline (PAX), a compound synthesized by Penicillium paxilli, has been known as a specific antagonist of large conductance Ca2+-activated K+ Channels (BKCa). Here, we report the presence of PAX in the secretions of tree frogs (Hyla japonica) and that this compound has a novel function of inhibiting the potassium channel subfamily K member 18 (KCNK18) channels of their predators. The PAX-induced KCNK18 inhibition is sufficient to evoke Ca2+ influx in charybdotoxin-insensitive DRG neurons of rats. By forming pi-pi stacking interactions, four phenylalanines located in the central pore of KCNK18 stabilize PAX to block the ion permeation. For PAX-mediated toxicity, our results from animal assays suggest that the inhibition of KCNK18 likely acts synergistically with that of BKCa to elicit tingling and buzzing sensations in predators or competitors. These results not only show the molecular mechanism of PAX-KCNK18 interaction, but also provide insights into the defensive effects of the enriched PAX.
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页数:10
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