A Conserved Role for Stomatin Domain Genes in Olfactory Behavior

The highly-conserved stomatin domain has been identified in genes throughout all classes of life. In animals, different stomatin domain-encoding genes have been implicated in the function of the kidney, red blood cells, and specific neuron types, although the underlying mechanisms remain unresolved. In one well-studied example of stomatin do-main gene function, the Caenorhabditis elegans gene mec-2 and its mouse homolog Stoml3 are required for the function of mechanosensory neurons, where they modulate the activity of mechanosensory ion channels on the plas-ma membrane. Here, we identify an additional shared function for mec-2 and Stoml3 in a very different sensory context, that of olfaction. In worms, we find that a subset of stomatin domain genes are expressed in olfactory neurons, but only mec-2 is strongly required for olfactory behavior. mec-2 acts cell-autonomously and multiple alternatively-spliced isoforms of mec-2 can be substituted for each other. We generate a Stoml3 knock-out (KO) mouse and demonstrate that, like its worm homolog mec-2 , it is required for olfactory behavior. In mice, Stoml3 is not required for odor detection, but is required for odor discrimination. Therefore, in addition to their shared roles in mechanosensory behavior, mec-2 and Stoml3 also have a shared role in olfactory behavior.Significance StatementIn this manuscript we reveal a surprising moonlighting function for the conserved stomatin domain genes mec-2 (worm) and Stoml3 (mouse). Both factors have previously been studied extensively for their roles in mediating touch sensation in mechanosensory neurons. Here, we demonstrate that, in both worms and mice, they play an additional previously-unappreciated role in a different sensory modality, that of olfaction.

Automated summary

The highly-conserved stomatin domain has been identified in genes throughout all classes of life. In one well-studied example, the Caenorhabditis elegans gene mec-2 and its mouse homolog Stoml3 are required for the function of mechanosensory neurons, and they also play a shared role in olfactory behavior.