Cathedrals inside you
August 1, 2016 4:09 PM Subscribe
Vaults are large, barrel shaped protein complexes. Found in most eukaryotic cells, their exact function is currently unknown.
UCLA's Rome Lab has more information about what we do know, and is even investigating their potential use as a drug delivery system.
UCLA's Rome Lab has more information about what we do know, and is even investigating their potential use as a drug delivery system.
If I read this correctly, it is being suggested that these are a microscopic life form that resides within all living cells?
posted by Foci for Analysis at 4:38 PM on August 1, 2016
posted by Foci for Analysis at 4:38 PM on August 1, 2016
Foci for Analysis: If I read this correctly, it is being suggested that these are a microscopic life form that resides within all living cells?
No, Vaults are just large protein structures. Nobody is suggesting they are discrete living things, not even to the point of being organelles of endosymbiotic origin, like mitochondria or plastids. They're just cellular parts. Also, they're not found in all living cells; no prokaryotes are known to have them and many eukaryotes seem to have lost them.
The interesting story here is that there is a cellular component within the living cells of many, many organisms, which nobody can find the purpose of. You can produce mice that don't have them and those mice don't seem to be different in any obvious way, yet the fact that it is conserved in a functional matter within large parts of the eukaryote tree means it must have significant evolutionary value, or it would have been removed by genetic drift. So it's quite the mystery.
posted by Mitrovarr at 5:08 PM on August 1, 2016 [18 favorites]
No, Vaults are just large protein structures. Nobody is suggesting they are discrete living things, not even to the point of being organelles of endosymbiotic origin, like mitochondria or plastids. They're just cellular parts. Also, they're not found in all living cells; no prokaryotes are known to have them and many eukaryotes seem to have lost them.
The interesting story here is that there is a cellular component within the living cells of many, many organisms, which nobody can find the purpose of. You can produce mice that don't have them and those mice don't seem to be different in any obvious way, yet the fact that it is conserved in a functional matter within large parts of the eukaryote tree means it must have significant evolutionary value, or it would have been removed by genetic drift. So it's quite the mystery.
posted by Mitrovarr at 5:08 PM on August 1, 2016 [18 favorites]
It's the mark of the Elder Things, geeze!
posted by GenjiandProust at 5:24 PM on August 1, 2016 [1 favorite]
posted by GenjiandProust at 5:24 PM on August 1, 2016 [1 favorite]
I frikking *LOVE* vaults. I want to emphasize mitrovarr's point again.
The interesting story here is that there is a GIANT cellular component within the living cells of many, many organisms - and the biology of these organisms has been studied for tens of millions of person-hours - which nobody can find the purpose of.
Biology from a molecular perspective is the gift that keeps on giving!
posted by lalochezia at 5:29 PM on August 1, 2016 [4 favorites]
The interesting story here is that there is a GIANT cellular component within the living cells of many, many organisms - and the biology of these organisms has been studied for tens of millions of person-hours - which nobody can find the purpose of.
Biology from a molecular perspective is the gift that keeps on giving!
posted by lalochezia at 5:29 PM on August 1, 2016 [4 favorites]
Another look at vaults: Molecule of the Month
posted by armacy at 5:41 PM on August 1, 2016 [6 favorites]
posted by armacy at 5:41 PM on August 1, 2016 [6 favorites]
I hate to contaminate scientific discussion with religious awe but all I can really say to this, while not understanding 90% of what is being said, is: oh my god.
posted by turbid dahlia at 6:03 PM on August 1, 2016
posted by turbid dahlia at 6:03 PM on August 1, 2016
"... barrel shaped protein complexes... their exact function is currently unknown."
In my case they're used to store single malt.
posted by Hairy Lobster at 6:08 PM on August 1, 2016 [8 favorites]
In my case they're used to store single malt.
posted by Hairy Lobster at 6:08 PM on August 1, 2016 [8 favorites]
In my case they're used to store single malt.
My own personal theory is that Joseph built the vaults to store grain.
posted by sallybrown at 6:13 PM on August 1, 2016 [17 favorites]
My own personal theory is that Joseph built the vaults to store grain.
posted by sallybrown at 6:13 PM on August 1, 2016 [17 favorites]
Midichlorians? (Ducks)
posted by rikschell at 6:57 PM on August 1, 2016 [4 favorites]
posted by rikschell at 6:57 PM on August 1, 2016 [4 favorites]
*throws light saber*
posted by sexyrobot at 7:06 PM on August 1, 2016 [3 favorites]
posted by sexyrobot at 7:06 PM on August 1, 2016 [3 favorites]
the fact that it is conserved in a functional matter within large parts of the eukaryote tree means it must have significant evolutionary value
Not to mention the energetic cost of generating a massive-molecular-weight protein complex...
Bummer that they're not in yeast, worm, or fly, though. It would make screening a lot easier. (FWIW, I have a PhD in molecular biology and hadn't heard of vaults before this post -- no doubt partially because I did my thesis on a model organism that doesn't have them!)
posted by en forme de poire at 7:33 PM on August 1, 2016 [7 favorites]
Not to mention the energetic cost of generating a massive-molecular-weight protein complex...
Bummer that they're not in yeast, worm, or fly, though. It would make screening a lot easier. (FWIW, I have a PhD in molecular biology and hadn't heard of vaults before this post -- no doubt partially because I did my thesis on a model organism that doesn't have them!)
posted by en forme de poire at 7:33 PM on August 1, 2016 [7 favorites]
en forme de poire: Not to mention the energetic cost of generating a massive-molecular-weight protein complex...
That doesn't hurt either. But think of the evolutionary distance this thing covered! Humans have at least a few half-functional or non-functional biochemical pathways. Nature is sloppy on the short scale and some broken stuff, or useless stuff, can linger for a bit before drift mutates it away. But nothing is going to make it all the way up from the stem Eukarya to goddamn Primates in functional, or indeed recognizable condition, unless it is really important. Maybe it's only important on the macro level, and it may not matter to every species (hence the loss in many lineages), but it must be important on some level to survive that kind of timescale.
posted by Mitrovarr at 9:37 PM on August 1, 2016 [5 favorites]
That doesn't hurt either. But think of the evolutionary distance this thing covered! Humans have at least a few half-functional or non-functional biochemical pathways. Nature is sloppy on the short scale and some broken stuff, or useless stuff, can linger for a bit before drift mutates it away. But nothing is going to make it all the way up from the stem Eukarya to goddamn Primates in functional, or indeed recognizable condition, unless it is really important. Maybe it's only important on the macro level, and it may not matter to every species (hence the loss in many lineages), but it must be important on some level to survive that kind of timescale.
posted by Mitrovarr at 9:37 PM on August 1, 2016 [5 favorites]
The first, most comprehensive, and in depth link, to a 2014 article in The Scientist, seemed to say that insects in general lack vaults:
If it is most or all insects, then I wonder whether a thing about insects which has always amazed me could offer a clue as to the function of vaults, when considered together with the identity of the third vault protein -- which is the only payload (as opposed to shell, or payload binding) protein of the vaults -- and the other place the third vault protein also appears
This inordinate abundance of insect species strongly suggests that insects could have a much greater tendency to produce species-generating mutants than other animal groups with similar reproductive patterns, and what that has to do with vaults is that the other place the third vault protein (TEP1) appears is in the telomerase complex, and the telomerase complex is crucially involved in integrating chromosomes into cell cytoskeletons and making it possible for cells to divide and maintain the integrity and proper number of chromosomes.
However, TEP1 knockout mice show that the telomerase complex can get along fine without TEP1 under normal circumstances, so TEP1 has at most a backup/failsafe function, but that can often be very important in biological systems.
And if TEP1 is part of a telomerase backup, then the vaults could be an important component which supplies fresh TEP1 and improves the efficacy of that failsafe.
And if the telomerase complex did fail during the process of sperm or egg production, you could end up with a fertilized egg with big changes in the arrangement and numbers of chromosomes, and such changes, in the very rare instances where they produce viable individuals, are very effective at generating new species.
In short, I think that the fact that there are so many species of insects, and that insects lack vaults (if they do, in fact), could point to maintenance of chromosome integrity as part of a telomerase complex failsafe, as a possible function for the vaults in general.
posted by jamjam at 10:25 PM on August 1, 2016 [6 favorites]
As Kedersha’s early analyses suggested, vaults are composed of multiple copies of at least four distinct components: three proteins and one RNA molecule. The major vault protein (MVP) accounts for some 75 percent of the particles’ mass, with each vault containing 78 copies of the protein. In fact, the expression of MVP in an insect cell line—insects themselves are one of the few eukaryotic organisms that don’t have vaults—results in the spontaneous formation of particles with morphologic characteristics similar to those of endogenous vaults.2 Another protein typically found in vaults is vault poly(ADP-ribose) polymerase (VPARP). VPARP and MVP mRNA transcripts are expressed in similar patterns in the cell, and subcellular fractionation studies point to a strong binding between the two proteins.[my emphasis]but the other links which address that issue seem to imply that mainly only fruit flies among insects lack them.
If it is most or all insects, then I wonder whether a thing about insects which has always amazed me could offer a clue as to the function of vaults, when considered together with the identity of the third vault protein -- which is the only payload (as opposed to shell, or payload binding) protein of the vaults -- and the other place the third vault protein also appears
The third vault protein is TEP1, previously identified as the mammalian telomerase-associated protein 1, which binds RNA in the telomerase complex. TEP1-knockout mice exhibited no alterations in telomerase function, suggesting its role in the nucleus is redundant, but vaults purified from these animals revealed a complete absence of the fourth component of vaults: vault RNA (vRNA), a small untranslated RNA found at the tips of the particles. This work pointed to TEP1’s role in the recruitment and stabilization of vRNA.The number of species of insects is startlingly larger than the number of species of all other animal groups put together -- in fact, according to my link, ~3/4 of all animal species are insects.
This inordinate abundance of insect species strongly suggests that insects could have a much greater tendency to produce species-generating mutants than other animal groups with similar reproductive patterns, and what that has to do with vaults is that the other place the third vault protein (TEP1) appears is in the telomerase complex, and the telomerase complex is crucially involved in integrating chromosomes into cell cytoskeletons and making it possible for cells to divide and maintain the integrity and proper number of chromosomes.
However, TEP1 knockout mice show that the telomerase complex can get along fine without TEP1 under normal circumstances, so TEP1 has at most a backup/failsafe function, but that can often be very important in biological systems.
And if TEP1 is part of a telomerase backup, then the vaults could be an important component which supplies fresh TEP1 and improves the efficacy of that failsafe.
And if the telomerase complex did fail during the process of sperm or egg production, you could end up with a fertilized egg with big changes in the arrangement and numbers of chromosomes, and such changes, in the very rare instances where they produce viable individuals, are very effective at generating new species.
In short, I think that the fact that there are so many species of insects, and that insects lack vaults (if they do, in fact), could point to maintenance of chromosome integrity as part of a telomerase complex failsafe, as a possible function for the vaults in general.
posted by jamjam at 10:25 PM on August 1, 2016 [6 favorites]
Not sure I'm doing my math right, but if each vault is 13 megadaltons and there can be as many as 100,000 in a single cell, that's a total of around 2x10^-12 grams, which is about the weight of the entire human DNA genome, and maybe around 1% of the entire dry cell weight. I can see why a smaller organism might want to jettison the weight and effort of creating all that if it only costs a few percent of fitness. It might also explain the odd coincidence that so many model organisms seem to lack them despite their overall prevalence, since scientists seem to prefer relatively smaller and simpler organisms as models.
posted by chortly at 11:20 PM on August 1, 2016 [1 favorite]
posted by chortly at 11:20 PM on August 1, 2016 [1 favorite]
Using proteins of completely unknown function as therapeutics because they can hold stuff is not a great strategy.
posted by benzenedream at 7:36 AM on August 2, 2016 [3 favorites]
posted by benzenedream at 7:36 AM on August 2, 2016 [3 favorites]
Still reading the articles, but boy, that looks like a nice little micro-environment to do some protein folding.
posted by maryr at 11:21 AM on August 2, 2016
posted by maryr at 11:21 AM on August 2, 2016
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posted by lucidium at 4:13 PM on August 1, 2016