Keep the cool feeling: A lipid enzyme for maintaining cool temperature sensation and avoidance

Thermal receptors called ionotropic receptors (IRs), specifically IR25a and IR21a, function in cool temperature-sensing neurons in larval head, known as dorsal organ cool cells (DOCCs), to mediate cool temperature avoidance. This behavior is affected by expression changes of IR25a and IR21a, but the underlying mechanism has been unknown. Takaaki Sokabe and his colleague Xiangmei Deng at the Exploratory Research Center on Life and Living Systems (ExCELLS) identified a monoacylglycerol acyltransferase (MGAT)-coding gene named bishu-1 as an important factor for maintaining the transcriptional level of IR25a and IR21a and the cooling responsiveness of DOCCs, thereby enabling the cool temperature sensation and avoidance. They recently published their findings in Communications Biology.

"The finding of bishu-1 was coincidental. MGATs are well known for their role in the energy storage processes in liver or intestine, so we didn't expect an essential role of its coding gene bishu-1 in thermal sensation initially," says Deng. "After observing that the mutants seemingly avoided warm temperatures, we gave a new name to the gene, bishu, which is a Chinese word for 'summering', describing the escaping behavior of larvae from heat."

Unlike other known lipid enzymes that have more direct interactions with sensory receptors through binding with their lipid metabolites or propagation of the physicochemical properties of the cell membranes, bishu-1 regulates the expression of receptor genes: bishu-1 proved important for the expression of transcription factor broad, which binds to the regulatory region of IR25a gene. Indeed, broad overexpression was sufficient to rescue the bishu-1 mutant's defects in cooling responses in DOCCs and cool temperature avoidance behaviors in larvae.

"Regulation of gene expression levels represents a novel role for lipid metabolism in the nervous system," Sokabe says. "broad is widely expressed in neurons, and numerous studies have reported the function of IRs in chemical, thermal, and humidity sensation. Since we have identified other MGAT-coding genes tandemly clustered on the genome, it will be interesting to examine how these lipid enzyme-mediated mechanisms affect multiple sensory processes."

This work could promote the discovery of lipid-mediated treatment for maintaining thermosensation and other sensory systems in humans.