The Vam6 and Gtr1-Gtr2 pathway activates TORC1 in response to amino acids in fission yeast

The Rag family of GTPases has been implicated in the TORC1 activation in Drosophila and in mammalian cells in response to amino acids. We have investigated the role of the Rag GTPases Gtr1 and Gtr2 in TORC1 regulation in Schizosaccharomyces pombe. Fission yeast Gtr1 and Gtr2 are non-essential proteins that enhance cell growth in the presence of amino acids in the medium. The function of Gtr1 and Gtr2 in nutrient signaling is further supported by the observation that even in rich medium the deletion of either gene results in the promotion of mating, meiosis and sporulation, consistent with the downregulation of TORC1. We show that Gtr1 and Gtr2 colocalize with TORC1 in vacuoles, where TORC1 is presumably activated. Epistasis analyses indicated that Gtr1 and Gtr2 function downstream of Vam6 and upstream of TORC1 in response to amino acid signals. Our data demonstrate the existence of an evolutionarily conserved pathway with the Vam6 and Gtr1-Gtr2 pathway activating TORC1, which in turns stimulates cell growth and inhibits sexual differentiation. © 2012.This work is supported by grants from Ministerio de Economía y Competitividad [grant numbers BFU2008-01808, BFU2011-28274, Consolider CSD2007-00015] and Junta de Castilla y León Grupo de Excelencia [grant number GR 265] to S.M. N.V. is supported by a postdoctoral grant from the Carlos III Institute, Ministerio de Sanidad.Peer Reviewe