TY - JOUR
T1 - Negative regulation of amino acid signaling by MAPK-regulated 4F2hc/Girdin complex
AU - Weng, Liang
AU - Han, Yi Peng
AU - Enomoto, Atsushi
AU - Kitaura, Yasuyuki
AU - Nagamori, Shushi
AU - Kanai, Yoshikatsu
AU - Asai, Naoya
AU - An, Jian
AU - Takagishi, Maki
AU - Asai, Masato
AU - Mii, Shinji
AU - Masuko, Takashi
AU - Shimomura, Yoshiharu
AU - Takahashi, Masahide
N1 - Publisher Copyright:
© 2018 Weng et al.
PY - 2018/3/14
Y1 - 2018/3/14
N2 - Amino acid signaling mediated by the activation of mechanistic target of rapamycin complex 1 (mTORC1) is fundamental to cell growth and metabolism. However, how cells negatively regulate amino acid signaling remains largely unknown. Here, we show that interaction between 4F2 heavy chain (4F2hc), a subunit of multiple amino acid transporters, and the multifunctional hub protein girders of actin filaments (Girdin) down-regulates mTORC1 activity. 4F2hc interacts with Girdin in mitogen-activated protein kinase (MAPK)- and amino acid signaling–dependent manners to translocate to the lysosome. The resultant decrease in cell surface 4F2hc leads to lowered cytoplasmic glutamine (Gln) and leucine (Leu) content, which down-regulates amino acid signaling. Consistently, Girdin depletion augments amino acid-induced mTORC1 activation and inhibits amino acid deprivation–induced autophagy. These findings uncovered the mechanism underlying negative regulation of amino acid signaling, which may play a role in tightly regulated cell growth and metabolism.
AB - Amino acid signaling mediated by the activation of mechanistic target of rapamycin complex 1 (mTORC1) is fundamental to cell growth and metabolism. However, how cells negatively regulate amino acid signaling remains largely unknown. Here, we show that interaction between 4F2 heavy chain (4F2hc), a subunit of multiple amino acid transporters, and the multifunctional hub protein girders of actin filaments (Girdin) down-regulates mTORC1 activity. 4F2hc interacts with Girdin in mitogen-activated protein kinase (MAPK)- and amino acid signaling–dependent manners to translocate to the lysosome. The resultant decrease in cell surface 4F2hc leads to lowered cytoplasmic glutamine (Gln) and leucine (Leu) content, which down-regulates amino acid signaling. Consistently, Girdin depletion augments amino acid-induced mTORC1 activation and inhibits amino acid deprivation–induced autophagy. These findings uncovered the mechanism underlying negative regulation of amino acid signaling, which may play a role in tightly regulated cell growth and metabolism.
UR - http://www.scopus.com/inward/record.url?scp=85045149103&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85045149103&partnerID=8YFLogxK
U2 - 10.1371/journal.pbio.2005090
DO - 10.1371/journal.pbio.2005090
M3 - Article
C2 - 29538402
AN - SCOPUS:85045149103
SN - 1544-9173
VL - 16
JO - PLoS Biology
JF - PLoS Biology
IS - 3
M1 - e2005090
ER -