Lysosomal exocytosis in Schwann cells contributes to axon remyelination
Lysosomal exocytosis in Schwann cells contributes to axon remyelination
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雪旺细胞中的溶酶体胞吐作用有助于轴突髓鞘再生
DOI：
10.1002/glia.21263
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发表时间：
2012-02-01
期刊：
影响因子：
6.2
通讯作者：
Gu, Xiaosong
中科院分区：
文献类型：
--
作者：
Chen, Gang;Zhang, Zhijun;Gu, Xiaosong
髓磷脂的生物合成是一个复杂的过程，涉及协同胞吐、胞吞、mRNA转运和细胞骨架动力学。虽然髓鞘异常在溶酶体贮积病中很常见，但我们对溶酶体在髓鞘形成和维持中的作用的理解仍然有限。在这里，我们发现施万细胞中的晚期内体/溶酶体含有丰富的髓鞘蛋白P0，它占周围神经系统致密髓鞘总蛋白的一半以上，并在响应各种刺激时表现出Ca 2+依赖性胞吐作用。Rab 27 a是一种分泌性溶酶体向质膜运输所需的小GTP酶，下调Rab 27 a在很大程度上阻断了许旺细胞中的溶酶体胞吐作用，并减少了再生坐骨神经的髓鞘再生。这些研究结果突出了一个新的作用，在雪旺细胞中的溶酶体，并建议在雪旺细胞中的调节溶酶体胞吐可能有重要的生理和病理意义的周围神经系统。© 2011 Wiley Periodicals，Inc.
Myelin biogenesis is a complex process involving coordinated exocytosis, endocytosis, mRNA transport, and cytoskeletal dynamics. Although abnormalities of myelin are common in lysosomal storage diseases, our understanding of the role of lysosomes in the formation and maintenance of myelin is still limited. Here, we show that late endosomes/lysosomes in Schwann cells contain abundant myelin protein P0, which accounts for over half the total protein of compact myelin in the peripheral nervous system and exhibit Ca2+‐dependent exocytosis in response to various stimuli. Downregulation of Rab27a, a small GTPase required for the trafficking of the secretory lysosomes to the plasma membrane, largely blocked lysosomal exocytosis in Schwann cells and reduced the remyelination of regenerated sciatic nerve. These findings highlight a novel role for lysosomes in Schwann cells and suggest that the regulated lysosome exocytosis in Schwann cells may have important physiological and pathological significance in the peripheral nervous system. © 2011 Wiley Periodicals, Inc.