Yamazaki Reiji, Ishibashi Tomoko, Baba Hiroko, Yamaguchi Yoshihide
Department of Molecular Neurobiology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
Department of Molecular Neurobiology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan
ASN Neuro. 2016 Sep 21;8(5). doi: 10.1177/1759091416669609. Print 2016 Oct.
Myelin is a special multilamellar structure involved in various functions in the nervous system. In the central nervous system, the oligodendrocyte (OL) produces myelin and has a unique morphology. OLs have a dynamic membrane sorting system associated with cytoskeletal organization, which aids in the production of myelin. Recently, it was reported that the assembly and disassembly of actin filaments is crucial for myelination. However, the partner myosin molecule which associates with actin filaments during the myelination process has not yet been identified. One candidate myosin is unconventional myosin ID (Myo1d) which is distributed throughout central nervous system myelin; however, its function is still unclear. We report here that Myo1d is expressed during later stages of OL differentiation, together with myelin proteolipid protein (PLP). In addition, Myo1d is distributed at the leading edge of the myelin-like membrane in cultured OL, colocalizing mainly with actin filaments, 2',3'-cyclic nucleotide phosphodiesterase and partially with PLP. Myo1d-knockdown with specific siRNA induces significant morphological changes such as the retraction of processes and degeneration of myelin-like membrane, and finally apoptosis. Furthermore, loss of Myo1d by siRNA results in the impairment of intracellular PLP transport. Together, these results suggest that Myo1d may contribute to membrane dynamics either in wrapping or transporting of myelin membrane proteins during formation and maintenance of myelin.
髓磷脂是一种特殊的多层结构，参与神经系统的多种功能。在中枢神经系统中，少突胶质细胞（OL）产生髓磷脂并具有独特的形态。OL具有与细胞骨架组织相关的动态膜分选系统，这有助于髓磷脂的产生。最近，有报道称肌动蛋白丝的组装和解聚对髓鞘形成至关重要。然而，在髓鞘形成过程中与肌动蛋白丝结合的伴侣肌球蛋白分子尚未被鉴定出来。一种候选肌球蛋白是非传统肌球蛋白ID（Myo1d），它分布于整个中枢神经系统髓磷脂中；然而，其功能仍不清楚。我们在此报告，Myo1d在OL分化的后期与髓磷脂蛋白脂蛋白（PLP）一起表达。此外，Myo1d分布于培养的OL中类髓鞘膜的前沿，主要与肌动蛋白丝、2',3'-环核苷酸磷酸二酯酶共定位，部分与PLP共定位。用特异性小干扰RNA敲低Myo1d会诱导显著的形态学变化，如突起回缩和类髓鞘膜退化，最终导致细胞凋亡。此外，小干扰RNA导致的Myo1d缺失会损害细胞内PLP的运输。总之，这些结果表明，Myo1d可能在髓磷脂形成和维持过程中，对髓鞘膜蛋白的包裹或运输过程中的膜动力学发挥作用。
