Dynamic Palmitoylation of STX11 Facilitates Injury-induced Fatty Acid Uptake to Promote Muscle Regeneration Wang et al

Different types of cells uptake fatty acids in response to different stimuli or physiological conditions; however, little is known about context-specific regulation of fatty acid uptake. Here, we show that muscle injury induces fatty acid uptake in muscle stem cells (MuSCs) to promote their proliferation and muscle regeneration. In human and mice, fatty acids are mobilized after muscle injury. Through CD36, fatty acids function as both fuels and growth signals to promote MuSC proliferation. Mechanistically, injury triggers the translocation of CD36 in MuSCs, which relies on dynamic palmitoylation of STX11. Palmitoylation facilitates the formation of STX11/SNAP23/VAMP4 SANRE complex, which stimulates the fusion of CD36- and STX11-containing vesicles. Restricting fatty acids supply, blocking fatty acid uptake, or inhibiting STX11 palmitoylation attenuates muscle regeneration. Our studies have identified a critical role of fatty acids in muscle regeneration and shed light on context-specific regulation of fatty acid sensing and uptake. The uploaded data include the uncropped images of the western blots.不同细胞会响应不同刺激或生理状态摄取脂肪酸，但目前对脂肪酸摄取的情境特异性调控机制尚不清楚。本研究发现，肌肉损伤可诱导肌肉干细胞（MuSCs）摄取脂肪酸，以促进其增殖与肌肉再生。在人类与小鼠体内，肌肉损伤后会发生脂肪酸动员。通过CD36蛋白，脂肪酸可同时作为能量底物与生长信号，促进MuSCs增殖。机制层面，肌肉损伤可触发MuSCs中CD36的转位，这一过程依赖于突触融合蛋白11（STX11）的动态棕榈酰化修饰。棕榈酰化修饰可促进STX11/SNAP23/囊泡相关膜蛋白4（VAMP4）SANRE复合物的形成，进而刺激携带CD36与STX11的囊泡融合。限制脂肪酸供给、阻断脂肪酸摄取或抑制STX11的棕榈酰化修饰，均可削弱肌肉再生能力。本研究明确了脂肪酸在肌肉再生中的关键作用，并为脂肪酸感知与摄取的情境特异性调控机制提供了新见解。上传的数据集包含未裁切的蛋白质免疫印迹（Western Blot）实验图像。