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 distinct tissues where they are expressed remain all-important unanswered questions. The nematode Caenorhabditis elegans has a single PIEZO ortholog (
pezo-1) predicted to have twelve isoforms. While all isoforms share many transmembrane domains, they differ in the number shared, particularly in those underlying the differences between PIEZO1 and PIEZO2 in mammals. Here we use translational and transcriptional reporters to show that long
pezo-1 isoforms are selectively expressed in mesodermally derived tissues (such as muscle and glands). We show that pharyngeal muscles, glands, and valve all rely on long
pezo-1 isoforms to respond appropriately to the presence of food. Specifically, we found that gland cell activation is modulated by food presence and density, but that in the absence of long isoforms of
pezo-1 gland cells had reduced activity that did not significantly respond to food. The number of
pezo-1 isoforms in C. elegans, their differential pattern of expression, and their role 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.