mTORC1 is activated when cells are fed with amino acids. New preprint with @robzonculab.bsky.social led by Rachel Jansen shows how the massive "CastiGATOR" complex is formed when arginine-free CASTOR1 binds to the GATOR2 complex to antagonize mTORC1 starved cells. tinyurl.com/yr6en6f4 - ThreadSky

jimhurley.bsky.social • 19 days ago

mTORC1 is activated when cells are fed with amino acids. New preprint with @robzonculab.bsky.social led by Rachel Jansen shows how the massive "CastiGATOR" complex is formed when arginine-free CASTOR1 binds to the GATOR2 complex to antagonize mTORC1 starved cells. https://tinyurl.com/yr6en6f4

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merz.bsky.social•18 days ago

Hi Jim! This is amazing. I see that you're working at 0 or 50mM Arg. I'm wondering if you know yet what the [Arg] affinity or apparent Km is, and whether there are signs of cooperativity?

jimhurley.bsky.social•18 days ago

You probably have some kind of cool hypothesis in mind... why do you ask?

merz.bsky.social•18 days ago

I'm interested entirely as an observer. I'm wondering whether the ensemble of these complexes act more as a switch, or a rheostat.

jimhurley.bsky.social•18 days ago

I didn't see it (Kd, nH) in Sabatini's papers on this and we didn't check yet, but we should. Good suggestion.

merz.bsky.social•18 days ago

Congratulations. Such beautiful work.

jimhurley.bsky.social•18 days ago

Thx. Do you ever make it back to Santa Cruz these days?

merz.bsky.social•18 days ago

Seldom. I have a few friends there but most family are now in WA, CO, and the mid-Atlantic.

merz.bsky.social•18 days ago

I do miss it, sometimes.

jimhurley.bsky.social•19 days ago

The key cell validation was done by Clement Maghe in @robzonculab.bsky.social

mcduncanlab.bsky.social•19 days ago

What is the deal with Sec13? Why is it in three distinct complexes?

lizmillercu.bsky.social•15 days ago

I think it's a clamp. Provides structural rigidity but via protein-protein interfaces so it might be dynamic/malleable. Four complexes (so far - not privilege to Alex's info): Sec31 (the OG and only essential function in yeast), Sec16 (function unknown), NPC, GATOR.

jimhurley.bsky.social•19 days ago

Sec13 is a nice building block for a cage, but why GATOR2 is a cage, we still have no idea. There is still a lot more to this puzzle to come.

merz.bsky.social•18 days ago

More than three complexes, I'm told ;).

mcduncanlab.bsky.social•18 days ago

Did I miss a publication or is this a forthcoming study. So curious now.

Sec13-the duct-tape of the cellular world.

merz.bsky.social•18 days ago

personal comm. from a mutual friend

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