The mechanistic target of rapamycin complex 1 (mTORC1) pathway is a key regulator of cell metabolism, growth and survival; this is especially important for cells with high metabolic rates, such as hepatocytes and epithelial cells. Although Rab GTPases, key regulators of trafficking events, have been shown to be involved in mTORC1 signalling, it is not fully understood how they affect different cell types. In their study, Micah Schott, Mark McNiven and colleagues (Drizyte-Miller et al., 2020) identify Rab32 as a new regulator of mTORC1 activity. Rab32 localises prominently to the acidic late endosomes and lysosomes in rat hepatocytes and Hep3B human hepatoma cells. Its knockdown decreases the activity of the p70 ribosomal protein S6 kinase (S6K), a target of mTORC1, leading to a decrease in cell proliferation, size and viability. Moreover, the authors demonstrate that Rab32 is necessary for amino-acid-induced mTORC1 activation, as well as for its activity under basal conditions. Accordingly, Rab32-depleted Hep3B cells display an increased number of lysosomes due to the activation of the transcription factor EB (TFEB), which is normally inhibited by mTORC1 signalling. Finally, the authors show that Rab32 interacts with mTOR in a GTP/GDP-independent manner, which enables its association with lysosomes, activating mTOR signalling. This study, thus, identifies a new role for Rab32 in the control of cellular growth and metabolism through the regulation of mTORC1 signalling.
Rab32 hops on the metabolic pathway
Rab32 hops on the metabolic pathway. J Cell Sci 1 June 2020; 133 (11): e1105. doi:
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