TY - JOUR
T1 - Phosphorylation of SNX27 by MAPK11/14 links cellular stress–signaling pathways with endocytic recycling
AU - Mao, Lejiao
AU - Liao, Chenyi
AU - Qin, Jiao
AU - Gong, Yanqiu
AU - Zhou, Yifei
AU - Li, Shasha
AU - Liu, Zhe
AU - Deng, Huaqing
AU - Deng, Wankun
AU - Sun, Qingxiang
AU - Mo, Xianming
AU - Xue, Yu
AU - Billadeau, Daniel D.
AU - Dai, Lunzhi
AU - Li, Guohui
AU - Jia, Da
N1 - Publisher Copyright:
© 2021 Mao et al.
PY - 2021/2
Y1 - 2021/2
N2 - Endocytosed proteins can be delivered to lysosomes for degradation or recycled to either the trans-Golgi network or the plasma membrane. It remains poorly understood how the recycling versus degradation of cargoes is determined. Here, we show that multiple extracellular stimuli, including starvation, LPS, IL-6, and EGF treatment, can strongly inhibit endocytic recycling of multiple cargoes through the activation of MAPK11/14. The stress-induced kinases in turn directly phosphorylate SNX27, a key regulator of endocytic recycling, at serine 51 (Ser51). Phosphorylation of SNX27 at Ser51 alters the conformation of its cargo-binding pocket and decreases the interaction between SNX27 and cargo proteins, thereby inhibiting endocytic recycling. Our study indicates that endocytic recycling is highly dynamic and can crosstalk with cellular stress–signaling pathways. Suppression of endocytic recycling and enhancement of receptor lysosomal degradation serve as new mechanisms for cells to cope with stress and save energy.
AB - Endocytosed proteins can be delivered to lysosomes for degradation or recycled to either the trans-Golgi network or the plasma membrane. It remains poorly understood how the recycling versus degradation of cargoes is determined. Here, we show that multiple extracellular stimuli, including starvation, LPS, IL-6, and EGF treatment, can strongly inhibit endocytic recycling of multiple cargoes through the activation of MAPK11/14. The stress-induced kinases in turn directly phosphorylate SNX27, a key regulator of endocytic recycling, at serine 51 (Ser51). Phosphorylation of SNX27 at Ser51 alters the conformation of its cargo-binding pocket and decreases the interaction between SNX27 and cargo proteins, thereby inhibiting endocytic recycling. Our study indicates that endocytic recycling is highly dynamic and can crosstalk with cellular stress–signaling pathways. Suppression of endocytic recycling and enhancement of receptor lysosomal degradation serve as new mechanisms for cells to cope with stress and save energy.
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U2 - 10.1083/JCB.202010048
DO - 10.1083/JCB.202010048
M3 - Article
C2 - 33605979
AN - SCOPUS:85102214966
SN - 0021-9525
VL - 220
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 4
M1 - e202010048
ER -