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.

不同类型的细胞可响应不同刺激或生理状态摄取脂肪酸，但目前学界对脂肪酸摄取的情境特异性调控机制仍知之甚少。本研究发现，肌肉损伤可诱导肌肉干细胞（muscle stem cells, MuSCs）摄取脂肪酸，进而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。脂肪酸通过CD36同时作为燃料与生长信号，促进MuSCs增殖。机制上，肌肉损伤触发MuSCs中CD36的转位，这一过程依赖于STX11的动态棕榈酰化。棕榈酰化可促进STX11/SNAP23/VAMP4 SANRE复合体的形成，进而刺激携带CD36与STX11的囊泡融合。限制脂肪酸供应、阻断脂肪酸摄取或抑制STX11棕榈酰化，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提供了新的研究思路。本次上传的数据包含未裁切的蛋白质免疫印迹（western blots）图像。