Lysosomal Exocytosis in Schwann Cells Contributes to Axon Remyelination

髓鞘形成是一个包括协同性的胞吐、内吞、mRNA转运和细胞骨架的动态变化的复杂过程。尽管髓鞘的异常在溶酶体贮积症中很常见,但对溶酶体在髓鞘形成和维持中所扮演的角色仍不清楚。本文发现Schwann细胞中的晚期内涵体/溶酶体包含大量的髓鞘蛋白P0,含量占超过一半的外周神经系统中的致密髓鞘的总蛋白并且在不同的刺激下表现出Ca2+依赖性的胞吐作用。Rab27a(一种将分泌溶酶体运输至细胞膜的小GTP酶)下调,极大地阻碍了Schwann细胞中的溶酶体胞吐作用,减少了再生坐骨神经的髓鞘形成。这些发现强调了Schwann细胞中溶酶体的新角色,提示调节Schwann细胞中的溶酶体胞吐作用在外周神经系统中有很重要的生理和病理意义。

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 Ca 2＋-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.2011Wiley Peroidicals,Inc.