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Biological Chemistry

Researchers trace the evolutionary origins of chemosensing in cephalopods

Their chemosensing receptors are descended from those that facilitate intercellular signaling in the nervous system

by Shi En Kim
April 14, 2023


A close-up of an octopus at the eye, ringed with sucker-dotted tentacles.
Credit: Anik Grearson, Peter Kilian
Octopus suckers contain chemosensing receptors that allow these hunters to taste by touch.

Evolution doesn’t manifest only as specialized beaks, wings, and other features across the animal kingdom. It also acts on the level of molecules. Take, for instance, a receptor protein serving as a gateway for chemical detection on the sucker of an octopus. It allows octopuses to essentially hunt via a ‘taste-by-touch’ strategy. This week, two new studies in the journal Nature show that the chemotactile receptors on cephalopods evolved from a ubiquitous protein with a very different job: to enable intercellular signaling in the nervous system.

“This [research] has opened up new territory for understanding how animals taste the world,” says Cliff Ragsdale, a neurobiologist at the University of Chicago who didn’t participate in the investigation.

The recent pair of studies, led by Harvard University physiologist Nicholas Bellono, started from a simple question: where did chemosensation in cephalopods come from? This question has also beguiled other researchers, who for decades have wondered how cephalopods sniff on the seafloor. In 2020, Bellono’s team identified the first family of chemotactile receptors on the suckers of octopuses (Cell, 2020, DOI: 10.1016/j.cell.2020.09.008). These receptors turn on when natural molecules in the environment bind to them, and they convert chemical cues into electrical ones.

Signaling receptors in the nervous system work the same way, relaying electrical dispatches between neurons when they are stimulated by neurotransmitters. In the new studies, the researchers compared the structures of chemotactile receptors to their ancestral nicotine acetylcholine receptors. As a first step, they solved the structures of the descendant proteins using cryo-electron microscopy. “The way something is built tells you a lot about how it would work,” says Ryan Hibbs, a structural biologist who worked on the project at the University of Texas Southwestern Medical Center before moving to the University of California San Diego.

The researchers were surprised to learn that the chemotactile receptor in modern octopuses had jettisoned its hydrophilic binding pocket. That means the modern receptor can no longer bind to its predecessor’s namesake neurotransmitter, the polar acetylcholine molecule. Instead, it prefers greasy compounds such as terpenes (Nature, 2023, DOI: 10.1038/s41586-023-05822-1).

Because polar molecules such as acetylcholine quickly dissipate in the ocean, octopuses would be more successful foragers if they sensed insoluble compounds that cling to surfaces and linger in aquatic environments—hence the adaptation of the sucker receptor from acetylcholine activation to a penchant for nonpolar molecules. “The structure gave us this clue about the different chemistries of activating molecules that made a heck of a lot of sense,” Hibbs says.

The second study of the pair revealed different adaptations in the receptors on squid suckers (Nature, 2023, DOI: 10.1038/s41586-023-05808-z). The ambush predators have receptors that hew closer to their nicotinic receptor origins to facilitate the detection of soluble, bitter molecules such as denatonium. This receptor rejiggering may have been the instigator of squids’ hunting quirk: snagging unsuspecting prey with their tentacles for a quick taste test before deciding whether to keep their prey or reject it.

Credit: Anik Grearson and Peter Kilian
Pajama squids are ambush predators. Their suckers contain receptors that can sense chemicals. This ability allows squids to taste their prey, such as shrimp, before deciding whether to keep it or reject it.

The new findings show that “receptor structures affect not only receptor function, but also open up new ecologies for animals,” Ragsdale says. He adds that the work could also one day aid engineers in designing underwater robots that can detect chemicals in their surroundings.


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