TY - JOUR
T1 - Cytosolic pH regulates cell growth through distinct gtpases, Arf1 and Gtr1, to promote ras/PKA and TORC1 activity
AU - Dechant, Reinhard
AU - Saad, Shady
AU - Ibáñez, Alfredo J.
AU - Peter, Matthias
PY - 2014/8/7
Y1 - 2014/8/7
N2 - Regulation of cell growth by nutrients is governed by highly conserved signaling pathways, yet mechanisms of nutrient sensing are still poorly understood. In yeast, glucose activates both the Ras/PKA pathway and TORC1, which coordinately regulate growth through enhancing translation and ribosome biogenesis and suppressing autophagy. Here, we show that cytosolic pH acts as a cellular signal to activate Ras and TORC1 in response to glucose availability. We demonstrate that cytosolic pH is sensitive to the quality and quantity of the available carbon source (C-source). Interestingly, Ras/PKA and TORC1 are both activated through the vacuolar ATPase (V-ATPase), which was previously identified as a sensor for cytosolic pH in vivo. V-ATPase interacts with two distinct GTPases, Arf1 and Gtr1, which are required for Ras and TORC1 activation, respectively. Together, these data provide a molecular mechanism for how cytosolic pH links C-source availability to the activity of signaling networks promoting cell growth.
AB - Regulation of cell growth by nutrients is governed by highly conserved signaling pathways, yet mechanisms of nutrient sensing are still poorly understood. In yeast, glucose activates both the Ras/PKA pathway and TORC1, which coordinately regulate growth through enhancing translation and ribosome biogenesis and suppressing autophagy. Here, we show that cytosolic pH acts as a cellular signal to activate Ras and TORC1 in response to glucose availability. We demonstrate that cytosolic pH is sensitive to the quality and quantity of the available carbon source (C-source). Interestingly, Ras/PKA and TORC1 are both activated through the vacuolar ATPase (V-ATPase), which was previously identified as a sensor for cytosolic pH in vivo. V-ATPase interacts with two distinct GTPases, Arf1 and Gtr1, which are required for Ras and TORC1 activation, respectively. Together, these data provide a molecular mechanism for how cytosolic pH links C-source availability to the activity of signaling networks promoting cell growth.
UR - http://www.scopus.com/inward/record.url?scp=84906101389&partnerID=8YFLogxK
U2 - 10.1016/j.molcel.2014.06.002
DO - 10.1016/j.molcel.2014.06.002
M3 - Article
C2 - 25002144
AN - SCOPUS:84906101389
SN - 1097-2765
VL - 55
SP - 409
EP - 421
JO - Molecular Cell
JF - Molecular Cell
IS - 3
ER -