mLST8
mLST8 (GbetaL) - a shared subunit of BOTH mTOR complexes. Especially required for mTORC2 to assemble and signal to Akt; largely dispensable for mTORC1.
A shared subunit that matters more to mTORC2. A small building block shared by both mTOR complexes, but it matters much more for mTORC2 - without it, mTORC2 can't properly assemble and signal to Akt, while mTORC1 mostly works fine without it.
Knockout phenocopies Rictor rather than Raptor loss, which is the standard genetic argument that mLST8 is an mTORC2-essential component.
TL;DR. mLST8 appears in 4 curated studies in Oliver's mTOR Atlas: 4 at the molecular level (cells, biochemistry, structure). No study in people is recorded for it in the Atlas yet. It has 1 interaction in the curated pathway model.
In the pathway model
| Interaction | Mechanism | Evidence | Studies |
|---|---|---|---|
| mLST8 required-for mTORC2 mechanism: complex-assembly · this link in full · on the map table | This protein isn't needed for mTORC1 in a living animal, but mTORC2 can't work without it – a clean genetic way to tell the two complexes apart. mLST8 is dispensable for mTORC1 in vivo but essential for mTORC2 - a rare clean genetic separation of the two complexes. mLST8 is dispensable for mTORC1 in vivo but essential for mTORC2 - a rare clean genetic separation of the two complexes. Holds under: Knockout mice (GUE2006) and human cell biochemistry (KIM2003). The separation of the two complexes is shown in mouse tissue; whether it holds in human tissue is not tested by these studies. plausible in people, not shown directly · settled in the literature | M | GUE2006, KIM2003 |
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| M | Molecular — cells, biochemistry, structure | 4 |
No direct human evidence in the Atlas for this entity yet — everything below rests on animal or molecular work.
Studies
| Year | Evidence | Study |
|---|---|---|
| 2016 | M | Tor forms a dimer through an N-terminal helical solenoid with a complex topology BAR2016 Cryo-EM shows TOR dimerizes through an N-terminal helical solenoid, informing mTORC1 architecture. |
| 2015 | M | Architecture of human mTOR complex 1 AYL2015 Cryo-EM architecture of human mTORC1 reveals its dimeric organization and active site access. |
| 2006 | M | Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1 GUE2006 The foundational genetic 'dissection' of the two complexes in living mice. Deleting Raptor was lethal early (mTORC1 essential); deleting Rictor or mLST8 selectively knocked out mTORC2 signaling to Akt and PKCalpha but spared S6K1. This cleanly assigned jobs to each complex and showed mLST8 is an mTORC2-specific requirement in mice. |
| 2003 | M | GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR KIM2003 Discovered mLST8 (GbetaL), the third core subunit that clamps onto mTOR's kinase domain and stabilizes the complex. It fine-tunes how tightly Raptor holds mTOR in response to nutrients - a small but essential cog that later turned out to be especially critical for the mTORC2 complex. |
Related entities
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