Schistosome TRPML channels play a role in neuromuscular activity and tegumental integrity.
Schistosome TRPML channels play a role in neuromuscular activity and tegumental integrity.
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血吸虫 TRPML 通道在神经肌肉活动和皮膜完整性中发挥作用。
DOI：
10.1016/j.biochi.2021.12.018
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发表时间：
2022-03
期刊：
影响因子：
3.9
通讯作者：
Greenberg RM
中科院分区：
文献类型：
--
作者：
Bais S;Norwillo A;Ruthel G;Herbert DR;Freedman BD;Greenberg RM
血吸虫病是由血吸虫属的寄生扁虫引起的一种被忽视的热带疾病。这种疾病的单药吡喹酮治疗存在挑战，如对未成熟蠕虫无效和无法预防再感染。重要的是，离子通道是许多当前驱虫剂的重要靶点。瞬时受体电位（Transient receptor potential， TRP）通道是感知信号的重要介质，对细胞功能和信号通路有显著影响。TRPML通道是一类表达于内溶酶体膜上的Ca2+渗透性TRP通道。它们调节溶酶体的功能和运输，以及其他功能。预测曼氏血吸虫具有一个TRPML基因（SmTRPML），两个剪接变体相差12个氨基酸。本研究的重点是探索SmTRPML通道的生理特性，以更好地了解其在血吸虫中的作用。在表达SmTRPML的哺乳动物细胞中，TRPML激活剂会引起细胞内Ca2+的升高。在这些细胞中，SmTRPML定位于溶酶体和质膜。这些相同的TRPML激活剂引起成虫运动的增加，这依赖于SmTRPML的表达，表明这些通道在寄生虫神经肌肉活动中起作用。抑制成虫体内的SmTRPML，或将成虫暴露于TRPML抑制剂中，会导致被皮空泡化、球囊样表面渗出物和膜起泡，这与其他生物体内TRPML缺失后的情况类似。总之，这些发现表明SmTRPML可能调节血吸虫内溶酶体系统的功能。此外，SmTRPML在神经肌肉活动和寄生虫被膜完整性中的作用使该通道成为抗血吸虫药物的候选靶点。
Schistosomiasis is a neglected tropical disease caused by parasitic flatworms of the genus Schistosoma. Mono-therapeutic treatment of this disease with the drug praziquantel, presents challenges such as inactivity against immature worms and inability to prevent reinfection. Importantly, ion channels are important targets for many current anthelmintics. Transient receptor potential (TRP) channels are important mediators of sensory signals with marked effects on cellular functions and signaling pathways. TRPML channels are a class of Ca2+-permeable TRP channels expressed on endolysosomal membranes. They regulate lysosomal function and trafficking, among other functions. Schistosoma mansoni is predicted to have a single TRPML gene (SmTRPML) with two splice variants differing by 12 amino acids. This study focuses on exploring the physiological properties of SmTRPML channels to better understand their role in schistosomes. In mammalian cells expressing SmTRPML, TRPML activators elicit a rise in intracellular Ca2+. In these cells, SmTRPML localizes both to lysosomes and the plasma membrane. These same TRPML activators elicit an increase in adult worm motility that is dependent on SmTRPML expression, indicating a role for these channels in parasite neuromuscular activity. Suppression of SmTRPML in adult worms, or exposure of adult worms to TRPML inhibitors, results in tegumental vacuolations, balloon-like surface exudates, and membrane blebbing, similar to that found following TRPML loss in other organisms. Together, these findings indicate that SmTRPML may regulate the function of the schistosome endolysosomal system. Further, the role of SmTRPML in neuromuscular activity and in parasite tegumental integrity establishes this channel as a candidate anti-schistosome drug target.
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影响因子：
14.2
作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
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发表时间：
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影响因子：
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作者：
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通讯作者：
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作者：
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影响因子：
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作者：
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通讯作者：
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