Cells in the mosquito’s gut drive its appetites
“The mosquito rectum is exactly as heavily studied as you might imagine,” Laura Duvall, a professor in Columbia’s department of Biological Sciences said in a recent conversation describing her new research. Which is to say, it barely has been.
Researchers have known for decades that female mosquitoes—the ones responsible for the itchy and irritating bites that can also transmit disease—lose their desire to bite humans for several days after feeding, as they digest blood and convert it to yolk protein that they deposit in their eggs.
The question has been why and how this happens. In a paper that Duvall wrote when she was a postdoc, she traced the lull in appetite to a receptor called Neuropeptide Y-like Receptor 7 (NPYLR7). Destroy the receptor, and mosquitoes never feel full: they continue to be attracted to humans even after they feed on our blood.
That paper was the jumping off point for Duvall’s newest research, published today in the journal Current Biology. Duvall and her team wanted to learn more about how NPYLR7 functions. They hypothesized that the receptor would be found in tissues all over the mosquito’s body, and expected to find it in the brain, where it lives in many other animals. “When you think about how much this receptor controls behavior, the brain is a natural place to look,” Duvall said. But their findings led them to the rectum.
The findings contribute to a growing body of research that shows that, across species, the gut is responsible for more than just clearing waste, and is actually helping regulate and control behavior.
Duvall connected the findings to GLP-1 agonists that have come to market recently as weight loss medications. GLP-1 is a peptide released by the gut that plays an important role in signaling fullness in humans, similar to the molecules that activate NPYLR7 in mosquitoes. “In both cases we see peptides playing a very important role, in conversation with the nervous system, and driving how and when eating occurs,” Duvall said.
“We’re studying mosquitoes, but it’s contributing to a larger theme, which is that signaling from the gut is more complex than we’d appreciated and more important for behavior than we’d realized, across species,” Duvall said.
To better understand how the rectal cells interacted with the mosquito’s nervous system, the researchers used a fluorescent protein that glows when calcium levels rise. After mosquitos eat, nearby nerve cells release a peptide called RYamide that activates NYPLR7. The team showed that applying this peptide triggered calcium increases in the rectal cells, much like the response seen in neurons. They observed that after NYPLR7 was activated, rectal cells showed changes suggesting that they release signaling packets back to the nervous system. In other words, the rectal cells almost behaved like neurons—like part of the nervous system itself.
“One possibility is that these cells are actually positioned in the rectum so that they can sense the nutrients that are available in the gut, and how full the mosquito is, giving a pretty good sense of what nutrients are available, and then sending that information back to the brain,” Duvall said.
The finding also has possible implications for how we develop ways to stop mosquitoes from biting us. “If you want to disrupt these receptors, you could potentially feed the mosquitoes something that would do so,” she said. “It’s a much more accessible target than a receptor in the brain.”
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Researchers have known for decades that female mosquitoes—the ones responsible for the itchy and irritating bites that can also transmit disease—lose their desire to bite humans for several days after feeding, as they digest blood and convert it to yolk protein that they deposit in their eggs.
The question has been why and how this happens. In a paper that Duvall wrote when she was a postdoc, she traced the lull in appetite to a receptor called Neuropeptide Y-like Receptor 7 (NPYLR7). Destroy the receptor, and mosquitoes never feel full: they continue to be attracted to humans even after they feed on our blood.
That paper was the jumping off point for Duvall’s newest research, published today in the journal Current Biology. Duvall and her team wanted to learn more about how NPYLR7 functions. They hypothesized that the receptor would be found in tissues all over the mosquito’s body, and expected to find it in the brain, where it lives in many other animals. “When you think about how much this receptor controls behavior, the brain is a natural place to look,” Duvall said. But their findings led them to the rectum.
The findings contribute to a growing body of research that shows that, across species, the gut is responsible for more than just clearing waste, and is actually helping regulate and control behavior.
Duvall connected the findings to GLP-1 agonists that have come to market recently as weight loss medications. GLP-1 is a peptide released by the gut that plays an important role in signaling fullness in humans, similar to the molecules that activate NPYLR7 in mosquitoes. “In both cases we see peptides playing a very important role, in conversation with the nervous system, and driving how and when eating occurs,” Duvall said.
“We’re studying mosquitoes, but it’s contributing to a larger theme, which is that signaling from the gut is more complex than we’d appreciated and more important for behavior than we’d realized, across species,” Duvall said.
To better understand how the rectal cells interacted with the mosquito’s nervous system, the researchers used a fluorescent protein that glows when calcium levels rise. After mosquitos eat, nearby nerve cells release a peptide called RYamide that activates NYPLR7. The team showed that applying this peptide triggered calcium increases in the rectal cells, much like the response seen in neurons. They observed that after NYPLR7 was activated, rectal cells showed changes suggesting that they release signaling packets back to the nervous system. In other words, the rectal cells almost behaved like neurons—like part of the nervous system itself.
“One possibility is that these cells are actually positioned in the rectum so that they can sense the nutrients that are available in the gut, and how full the mosquito is, giving a pretty good sense of what nutrients are available, and then sending that information back to the brain,” Duvall said.
The finding also has possible implications for how we develop ways to stop mosquitoes from biting us. “If you want to disrupt these receptors, you could potentially feed the mosquitoes something that would do so,” she said. “It’s a much more accessible target than a receptor in the brain.”
END