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Fig. 4 | Journal of Biomedical Science

Fig. 4

From: Amino acid-dependent control of mTORC1 signaling: a variety of regulatory modes

Fig. 4

Ca2+-mediated pathways of mTORC1 activation. a Leucine triggers the increase of intracellular Ca2+ concentrations ([Ca2+]i) and stimulates the kinase activity of hVps34. The rise in [Ca2+]i may be sensed by CaM. Leucine may also activate hVps34 via hVps15 and LRS. PI3P production by activated hVps34 results in recruitment of PLD1, producing PA, b Leucine may be sensed by GPCRs, which elevate [Ca2+]i through Ca2+ fluxes from the ER via SHP-2-PLCĪ²4-IP3R signaling, leading to mTORC1 activation. c The umami receptor, T1R1/T1R3, senses amino acids and increases [Ca2+]i in a VDCC-dependent manner via unknown mechanisms, leading to lysosomal translocation and activation of mTORC1. d TRPML1 mediates lysosomal Ca2+ release into the cytosol, resulting in a local and transient increase in [Ca2+]i, which might be sensed by CaM to activate mTORC1. In turn mTORC1 phosphorylates TRPML1 to negatively regulate its Ca2+ release activity. Such feedback loop possibly maintains lysosomal and cellular homeostasis during nutrient starvation

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