The stress-induced c-Jun N-terminal kinase (JNK) controls microtubule dynamics by enhancing both microtubule growth and rescues. Here, we show that upon cell stress, JNK directly phosphorylates the microtubule rescue factor CLIP-170 in its microtubule-binding domain to increase its rescue-promoting activity. Phosphomimetic versions of CLIP-170 enhance its ability to promote rescue events in vitro and in cells. Furthermore, while phosphomimetic mutations do not alter CLIP-170’s capability to form comets at growing microtubule ends, both phosphomimetic mutations and JNK activation increase the occurrence of CLIP-170 remnants on the microtubule lattice at the rear of comets. As the CLIP-170 remnants, which are potential sites of microtubule rescue, display a shorter lifetime when CLIP-170 is phosphorylated, we propose that instead of acting at the time of rescue occurrence, CLIP-170 would rather contribute in preparing the microtubule lattice for future rescues at these predetermined sites.

中文翻译：

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JNK 应激诱导的 CLIP-170 磷酸化促进微管救援

应激诱导的 c-Jun N 末端激酶 (JNK) 通过增强微管生长和拯救来控制微管动力学。在这里，我们发现，在细胞应激时，JNK 直接磷酸化其微管结合域中的微管救援因子 CLIP-170，以增加其救援促进活性。CLIP-170 的拟磷剂版本增强了其在体外和细胞内促进救援事件的能力。此外，虽然拟磷突变不会改变CLIP-170在生长的微管末端形成彗星的能力，但拟磷突变和JNK激活都会增加彗星后部微管晶格上CLIP-170残余物的出现。由于 CLIP-170 残余物是微管救援的潜在位点，当 CLIP-170 磷酸化时，其寿命较短，因此我们建议 CLIP-170 不应该在救援发生时发挥作用，而是有助于准备微管晶格以便将来在这些预定地点进行救援。