Phosphorylation of SNX27 by MAPK11/14 links cellular stress-signaling pathways with endocytic recycling.
Phosphorylation of SNX27 by MAPK11/14 links cellular stress-signaling pathways with endocytic recycling.
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MAPK11/14 磷酸化 SNX27 将细胞应激信号通路与内吞再循环联系起来
DOI：
10.1083/jcb.202010048
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发表时间：
2021-04-05
期刊：
影响因子：
--
通讯作者：
Jia D
中科院分区：
文献类型：
--
作者：
Mao L;Liao C;Qin J;Gong Y;Zhou Y;Li S;Liu Z;Deng H;Deng W;Sun Q;Mo X;Xue Y;Billadeau DD;Dai L;Li G;Jia D
蛋白质内吞循环如何响应环境线索而发生变化尚不清楚。Mao等人证明多重应激通过mapk11 /14介导的SNX27丝氨酸51位点磷酸化抑制内噬循环。SNX27的磷酸化降低了它与货物蛋白的结合并抑制了蛋白质的内吞循环。内吞蛋白可以被递送到溶酶体降解或再循环到反式高尔基网络或质膜。人们对货物的回收和降解是如何确定的仍然知之甚少。在这里，我们发现多种细胞外刺激，包括饥饿、LPS、IL-6和EGF处理，可以通过激活MAPK11/14强烈抑制多种货物的内吞循环。应激诱导的激酶反过来直接磷酸化SNX27的丝氨酸51 (Ser51)， SNX27是内吞循环的关键调节因子。SNX27 Ser51位点的磷酸化改变了其载货结合袋的构象，减少了SNX27与载货蛋白之间的相互作用，从而抑制了内吞循环。我们的研究表明，内吞循环是高度动态的，可以与细胞应激信号通路串扰。抑制内吞循环和增强受体溶酶体降解是细胞应对应激和节约能量的新机制。
How protein endocytic recycling changes in response to environmental cues is poorly understood. Mao et al. demonstrated that multiple stresses inhibited endocytic recycling via MAPK11/14-mediated phosphorylation of SNX27 at Ser51. Phosphorylation of SNX27 decreases its binding to cargo proteins and suppresses protein endocytic recycling. 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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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
DOI：
10.1083/jcb.201702137
发表时间：
2017-11-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
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Steinberg F
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3.3
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Chan AS;Clairfeuille T;Landao-Bassonga E;Kinna G;Ng PY;Loo LS;Cheng TS;Zheng M;Hong W;Teasdale RD;Collins BM;Pavlos NJ
通讯作者：
Pavlos NJ
通过质谱法进行蛋白质分析的凝胶内消化方法的更新。
影响因子：
3.4
作者：
Goodman JK;Zampronio CG;Jones AME;Hernandez-Fernaud JR
通讯作者：
Hernandez-Fernaud JR
影响因子：
16.6
作者：
Lenoir M;Ustunel C;Rajesh S;Kaur J;Moreau D;Gruenberg J;Overduin M
通讯作者：
Overduin M