4 ms·
This area is very much in my wheelhouse (both the biosynthetic process, and functions of mucins). They’re a pretty interesting biomolecule, present in all anima
by hirenj 2y ago
This area is very much in my wheelhouse (both the biosynthetic process, and functions of mucins). They’re a pretty interesting biomolecule, present in all animals (slightly different molecules in other branches of life).
It kind of surprises me that such a low fold-change in core1 synthase yields such a huge change in glycocalyx. Everything we know about this enzyme says it is an absolute rocket on substrates, so I can’t really see this process being enzyme-limited. There might be other (mouse specific) things going on here that this is scratching the surface on.
- menzoic 2y agoI’m also surprised that a slight change in C1GalT1 expression has such a big effect on the glycocalyx. That enzyme is notoriously high-capacity, so you’d think it runs at near-saturating levels most of the time. My hunch is that something else in the pathway is hitting a bottleneck, possibly a chaperone like Cosmc that’s needed for proper enzyme folding, or maybe there’s some substrate competition with parallel glycosylation pathways. Once that bottleneck is reached, even a small shift can have an outsized impact on final glycan structures. In mice specifically, there might be unique regulatory quirks that amplify this effect, and you end up with a dramatic change in the mucins even though the enzyme itself seems too powerful to be the limiting step.
- hirenj 2y agoYes, something along these lines, and maybe the other pathways as the most interesting possibility. I don’t know if there any reports of sTn in older mice, but that would be pretty wild.
- randall 2y agothanks for doing work on this and thanks for commenting on it on hn!!
- FollowingTheDao 2y agoCopper and calcium seem to stimulate some mucins.