4 ms·

Was it always a big mystery? Or did we think we understood it the whole time, but only just recently discovered that we actually didn't?

ncr100 4y ago
Mystery. According to the article and the paper we now have a clear understanding of how it works - the proteins in worms (which are similar to humans in their hearing structures) and their function. So, unless I misread it, we absolutely know how sound > neural impulse works. More: > The initial step in the sensory transduction pathway underpinning hearing and balance in mammals involves the conversion of force into the gating of a mechanosensory transduction channel1. Despite the profound socioeconomic impacts of hearing disorders and the fundamental biological significance of understanding mechanosensory transduction, the composition, structure and mechanism of the mechanosensory transduction complex have remained poorly characterized. Here we report the single-particle cryo-electron microscopy structure of the native transmembrane channel-like protein 1 (TMC-1) mechanosensory transduction complex isolated from Caenorhabditis elegans. The two-fold symmetric complex is composed of two copies each of the pore-forming TMC-1 subunit, the calcium-binding protein CALM-1 and the transmembrane inner ear protein TMIE. CALM-1 makes extensive contacts with the cytoplasmic face of the TMC-1 subunits, whereas the single-pass TMIE subunits reside on the periphery of the complex, poised like the handles of an accordion. A subset of complexes additionally includes a single arrestin-like protein, arrestin domain protein (ARRD-6), bound to a CALM-1 subunit. Single-particle reconstructions and molecular dynamics simulations show how the mechanosensory transduction complex deforms the membrane bilayer and suggest crucial roles for lipid–protein interactions in the mechanism by which mechanical force is transduced to ion channel gating. https://www.nature.com/articles/s41586-022-05314-8 https://www.nature.com/articles/s41586-022-05314-8
- swayvil 4y ago
  >So, unless I misread it, we absolutely know how sound > neural impulse works Am I being unclear? I asked : did we always consider it to be a mystery? Or did we have a different model before? (Which just recently got replaced by this new, better, model)
  - jcims 4y ago
    Read the first word of the reply you're questioning.
    - swayvil 4y ago
      But then he says all that other stuff.
- thelittleone 4y ago
  Wow. For some reason I had always assumed worms cannot hear.
  - vanderZwan 4y ago
    I never thought about it before but if someone had asked me I probably would have guessed the same - humans are probably biased to assume hearing must involve ears. OTOH, detection of mechanical vibrations seems like the kind of adaptation to evolve early. Hearing is in some sense just a refinement of that, so at the very least the groundwork for it must be old.
    - thelittleone 4y ago
      Remarkable nature. Whenever my daily problems get on top of me, I like to spend a moment to think about the absurd but beautiful reality that we creatures exist and that we're hurtling through space. And now... that worms can hear... in a way similar enough to humans.
  - myself248 4y ago
    Smell (chemical environment) was probably the "original" sense, followed quickly by touch (slow macro pressure) and hearing (fast micro pressure). Pretty much every animal has those, even if they lack the brains to do much sophisticated with them. Sight came way, way, way, way, way, way, way later. Encoding language in sounds is an even more recent innovation, in the grand scheme. This may also be why we have such trouble assigning words to smells, and you can't write a poem to replace a hug, for instance. They're processed by entirely different, and far more primal, parts of the brain than language.
etiam 4y ago
A good deal of this appears, in my opinion, to be the press release overselling what has been done in research with their employees involved now being published in Nature. The function on physical and physiological levels has largely been well understood and that knowledge still stands in the light of this publication. What the researchers are reporting appears to be a more detailed structural description of this sensory protein complex, and the additional structure information combined with simulations of known physics and chemistry in turn suggests additional detail about of how the "signal" occurs on the molecular level. Disclaimer that I didn't take time to read the whole thing now, but that's the gist of it from summaries and skimming. It is, with little doubt, some valuable pieces of information in the context Collective Knowledge of Mankind, and keeping large, complex, multipart molecular machines like this reasonably stable and normal for examination is arduous work, so I don't mean to denigrate the studies or the scientific paper, but as so often the way this is being spun in the press release is regrettable.

ncr100 4y ago

Mystery. According to the article and the paper we now have a clear understanding of how it works - the proteins in worms (which are similar to humans in their hearing structures) and their function. So, unless I misread it, we absolutely know how sound > neural impulse works. More: > The initial step in the sensory transduction pathway underpinning hearing and balance in mammals involves the conversion of force into the gating of a mechanosensory transduction channel1. Despite the profound socioeconomic impacts of hearing disorders and the fundamental biological significance of understanding mechanosensory transduction, the composition, structure and mechanism of the mechanosensory transduction complex have remained poorly characterized. Here we report the single-particle cryo-electron microscopy structure of the native transmembrane channel-like protein 1 (TMC-1) mechanosensory transduction complex isolated from Caenorhabditis elegans. The two-fold symmetric complex is composed of two copies each of the pore-forming TMC-1 subunit, the calcium-binding protein CALM-1 and the transmembrane inner ear protein TMIE. CALM-1 makes extensive contacts with the cytoplasmic face of the TMC-1 subunits, whereas the single-pass TMIE subunits reside on the periphery of the complex, poised like the handles of an accordion. A subset of complexes additionally includes a single arrestin-like protein, arrestin domain protein (ARRD-6), bound to a CALM-1 subunit. Single-particle reconstructions and molecular dynamics simulations show how the mechanosensory transduction complex deforms the membrane bilayer and suggest crucial roles for lipid–protein interactions in the mechanism by which mechanical force is transduced to ion channel gating. https://www.nature.com/articles/s41586-022-05314-8 https://www.nature.com/articles/s41586-022-05314-8

swayvil 4y ago
>So, unless I misread it, we absolutely know how sound > neural impulse works Am I being unclear? I asked : did we always consider it to be a mystery? Or did we have a different model before? (Which just recently got replaced by this new, better, model)
- jcims 4y ago
  Read the first word of the reply you're questioning.
  - swayvil 4y ago
    But then he says all that other stuff.
thelittleone 4y ago
Wow. For some reason I had always assumed worms cannot hear.
- vanderZwan 4y ago
  I never thought about it before but if someone had asked me I probably would have guessed the same - humans are probably biased to assume hearing must involve ears. OTOH, detection of mechanical vibrations seems like the kind of adaptation to evolve early. Hearing is in some sense just a refinement of that, so at the very least the groundwork for it must be old.
  - thelittleone 4y ago
    Remarkable nature. Whenever my daily problems get on top of me, I like to spend a moment to think about the absurd but beautiful reality that we creatures exist and that we're hurtling through space. And now... that worms can hear... in a way similar enough to humans.
- myself248 4y ago
  Smell (chemical environment) was probably the "original" sense, followed quickly by touch (slow macro pressure) and hearing (fast micro pressure). Pretty much every animal has those, even if they lack the brains to do much sophisticated with them. Sight came way, way, way, way, way, way, way later. Encoding language in sounds is an even more recent innovation, in the grand scheme. This may also be why we have such trouble assigning words to smells, and you can't write a poem to replace a hug, for instance. They're processed by entirely different, and far more primal, parts of the brain than language.

etiam 4y ago

A good deal of this appears, in my opinion, to be the press release overselling what has been done in research with their employees involved now being published in Nature. The function on physical and physiological levels has largely been well understood and that knowledge still stands in the light of this publication. What the researchers are reporting appears to be a more detailed structural description of this sensory protein complex, and the additional structure information combined with simulations of known physics and chemistry in turn suggests additional detail about of how the "signal" occurs on the molecular level. Disclaimer that I didn't take time to read the whole thing now, but that's the gist of it from summaries and skimming. It is, with little doubt, some valuable pieces of information in the context Collective Knowledge of Mankind, and keeping large, complex, multipart molecular machines like this reasonably stable and normal for examination is arduous work, so I don't mean to denigrate the studies or the scientific paper, but as so often the way this is being spun in the press release is regrettable.