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CNP过表达诱导少突胶质细胞膜异常,并抑制髓鞘碱性蛋白积累和髓鞘紧密化。

CNP overexpression induces aberrant oligodendrocyte membranes and inhibits MBP accumulation and myelin compaction.

作者信息

Yin X, Peterson J, Gravel M, Braun P E, Trapp B D

机构信息

Department of Neurosciences, The Cleveland Clinic Foundation, Ohio 44195, USA.

出版信息

J Neurosci Res. 1997 Oct 15;50(2):238-47. doi: 10.1002/(SICI)1097-4547(19971015)50:2<238::AID-JNR12>3.0.CO;2-4.

Abstract

2',3'-Cyclic nucleotide 3'-phosphodiesterase (CNP) is highly enriched in myelin-forming cells where it is concentrated at the cytoplasmic side of all surface membranes except those of compact myelin. Previous studies have provided evidence that CNP is functionally involved in migration or expansion of membranes during myelination. This hypothesis is supported, in part, by the production of aberrant myelin membranes in transgenic mice that have a 6-fold increase in CNP expression. In addition, many myelin lamellae in these CNP-overexpressing mice lacked major dense lines (MDLs). The purpose of the present study was to determine if CNP overexpression altered: (1) oligodendrocyte and myelin membrane production during early stages of myelination, and (2) the ultrastructural distribution of CNP and myelin basic protein (MBP) in myelin membranes. We identified aberrant membrane expanses that extended from premyelinating oligodendrocyte processes, the periaxonal membrane, and the contact point between oligodendrocyte processes and myelin internodes. Myelin membranes without MDLs were deficient in MBP and enriched in CNP. These data support a functional role for CNP during oligodendrocyte membrane expansion and indicate, for the first time, that CNP may help target MBP to compact myelin.

摘要

2',3'-环核苷酸3'-磷酸二酯酶(CNP)在形成髓鞘的细胞中高度富集,它集中在除紧密髓鞘外的所有表面膜的细胞质一侧。先前的研究已提供证据表明,CNP在髓鞘形成过程中在膜的迁移或扩展中发挥功能作用。这一假设部分得到了转基因小鼠中异常髓鞘膜产生的支持,这些小鼠的CNP表达增加了6倍。此外,这些过表达CNP的小鼠中的许多髓鞘板层缺乏主致密线(MDL)。本研究的目的是确定CNP过表达是否改变:(1)髓鞘形成早期少突胶质细胞和髓鞘膜的产生,以及(2)CNP和髓鞘碱性蛋白(MBP)在髓鞘膜中的超微结构分布。我们发现了从预髓鞘形成的少突胶质细胞突起、轴周膜以及少突胶质细胞突起与髓鞘节间的接触点延伸出的异常膜区域。没有MDL的髓鞘膜中MBP含量不足而CNP含量丰富。这些数据支持了CNP在少突胶质细胞膜扩展过程中的功能作用,并首次表明CNP可能有助于将MBP靶向到紧密髓鞘。

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