Distinct mechanoreceptor pezo-1 isoforms modulate food intake in the nematode Caenorhabditis elegans
Distinct mechanoreceptor pezo-1 isoforms modulate food intake in the nematode Caenorhabditis elegans
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DOI：
10.1093/g3journal/jkab429
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发表时间：
2022-03-01
影响因子：
2.6
通讯作者：
Vidal-Gadea, Andres G.
中科院分区：
文献类型：
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作者：
Hughes, Kiley;Shah, Ashka;Vidal-Gadea, Andres G.
已在哺乳动物中发现了两个 PIEZO 机械敏感阳离子通道 PIEZO1 和 PIEZO2，它们参与许多感觉过程。虽然结构相似，但 PIEZO 通道在不同的组织中表达并表现出独特的特性。不同的 PIEZO 如何传导力，它们的传导机制如何变化，以及它们独特的特性如何满足它们所表达的组织的功能需求仍然是所有重要的悬而未决的问题。线虫秀丽隐杆线虫有一个 PIEZO 直向同源物 (pezo-1)，预计有 12 个亚型。这些亚型共享许多跨膜结构域，但在哺乳动物中区分 PIEZO1 和 PIEZO2 的跨膜结构域有所不同。我们使用转录和翻译报告基因表明，紧邻长pezo-1亚型起始密码子上游的推定启动子序列主要驱动中胚层来源的组织（例如肌肉和腺体）中的绿色荧光蛋白（GFP）表达。相反，较短的 pezo-1 同种型上游序列导致 GFP 主要在神经元中表达。不同亚型上游的推定启动子驱动消化系统相同器官的不同细胞中的 GFP 表达。观察到的互补表达的独特模式表明，不同的亚型在这些器官内可能具有不同的功能。我们使用突变分析表明咽部肌肉和腺体需要长pezo-1亚型才能对食物的存在做出适当的反应。秀丽隐杆线虫中 pezo-1 同工型的数量、其假定的差异表达模式以及在实验可处理过程中的作用，使该系统成为研究 PIEZO 机械感受器家族成员之间功能差异的分子基础的有吸引力的系统。
Two PIEZO mechanosensitive cation channels, PIEZO1 and PIEZO2, have been identified in mammals, where they are involved in numerous sensory processes. While structurally similar, PIEZO channels are expressed in distinct tissues and exhibit unique properties. How different PIEZOs transduce force, how their transduction mechanism varies, and how their unique properties match the functional needs of the tissues they are expressed in remain all-important unanswered questions. The nematode Caenorhabditis elegans has a single PIEZO ortholog (pezo-1) predicted to have 12 isoforms. These isoforms share many transmembrane domains but differ in those that distinguish PIEZO1 and PIEZO2 in mammals. We used transcriptional and translational reporters to show that putative promoter sequences immediately upstream of the start codon of long pezo-1 isoforms predominantly drive green fluorescent protein (GFP) expression in mesodermally derived tissues (such as muscle and glands). In contrast, sequences upstream of shorter pezo-1 isoforms resulted in GFP expression primarily in neurons. Putative promoters upstream of different isoforms drove GFP expression in different cells of the same organs of the digestive system. The observed unique pattern of complementary expression suggests that different isoforms could possess distinct functions within these organs. We used mutant analysis to show that pharyngeal muscles and glands require long pezo-1 isoforms to respond appropriately to the presence of food. The number of pezo-1 isoforms in C. elegans, their putative differential pattern of expression, and roles in experimentally tractable processes make this an attractive system to investigate the molecular basis for functional differences between members of the PIEZO family of mechanoreceptors.