Biological complexity: touch and pressure sensing (Introduction)

by David Turell , Thursday, January 09, 2020, 18:44 (1780 days ago) @ David Turell

It requires huge complex ion pore proteins:

https://www.nature.com/articles/d41586-019-03955-w?utm_source=Nature+Briefing&utm_c...

"The discovery of Piezo2 and a related protein, Piezo1, was a high point in a decades-long search for the mechanisms that control the sense of touch. The Piezos are ion channels — gates in the cell membrane that allow ions to pass through — that are sensitive to tension. “We’ve learned a lot about how cells communicate, and it’s almost always been about chemical signalling,” says Ardem Patapoutian, a molecular neurobiologist at Scripps Research in La Jolla, California, whose group identified the Piezos. “What we’re realizing now is that mechanical sensation, this physical force, is also a signalling mechanism, and very little is known about it.”

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"Touch underlies the functioning of almost every tissue and cell type, says Patapoutian. Organisms interpret forces to understand their world, to enjoy a caress and to avoid painful stimuli. In the body, cells sense blood flowing past, air inflating the lungs and the fullness of the stomach or bladder. Hearing is based on cells in the inner ear detecting the force of sound waves.

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"One of the biggest questions is how the proteins, situated in the cell membrane, sense and respond to force. Using cryo-electron microscopy (cryo-EM), scientists have made progress in unravelling the Piezo channels’ bizarre, three-bladed structure, but a complete mechanism has been elusive.

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"Researchers were abuzz with the result, Goodman recalls, particularly because the Piezo proteins were so large and complex. Made of more than 2,500 amino acids and weighing a hefty 300 kilodaltons, Piezo1’s structure crosses the cell membrane a record-breaking 38 times. (For comparison, mammalian proteins typically contain closer to 500 amino acids.)

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"Fortunately, as Xiao was setting up his lab in 2013, another option for obtaining high-resolution structures was coming online: cryo-EM. His group used the method to report4 the first structure of Piezo1 in 2015, and since then, several higher-resolution versions have followed from Xiao’s group, MacKinnon’s, and Patapoutian’s. Last September, Xiao followed up with a picture of Piezo2, which is similar to Piezo1 in size and shape. Xiao’s picture of Piezo2 was the clearest view yet of the ends of the three blades, which move around and so are hard to capture5.

"The images were striking. Three Piezo proteins come together in a trimer that straddles the plasma membrane (see ‘Pressure sensors’). From the central pore, three arms spiral out like the blades on a propeller. They curve up and out, creating a deep divot in the surface of the cell.

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Comment: At this point please see the complexity of the diagrams

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“'The discovery of Piezos was a huge step forward for the whole field,” says Kate Poole, a biologist at the University of New South Wales in Sydney, Australia, but “it is also clear that the story is not just Piezos.”

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"Patapoutian’s team, meanwhile, is looking for entirely new channel families. In 2018, he, Murthy and Scripps structural biologist Andrew Ward reported what they think could be the largest group of mechanically activated channels. They knew of a protein family that helps plants to sense osmotic pressure — the OSCA proteins — and reasoned that they might sense force more generally. In human kidney cells, OSCAs did indeed respond to Murthy’s stretching of the cell membrane.

"The researchers also knew from previous studies that the OSCA proteins were closely related to another family of proteins in mammals, the TMEM63 proteins. TMEM63 channels from mice, humans and even fruit flies responded to stretch in Murthy’s assays, too, so OSCA and TMEM63 proteins make up a large family of force sensors that is common to many living things.

"The channels discovered so far cannot explain all instances of cellular mechano-sensitivity, says Murthy, now a biophysicist and neuroscientist at Oregon Health & Science University in Portland. More mechanosensors must be out there."

Comment: How much complexity must be demonstrated before it is fully accepted a designing brain is required to exist? And don't tell me infinity can do it. This universe is not infinitely old.