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两种mRNA的差异表达表明外周髓鞘蛋白PMP22在细胞生长和髓鞘形成中具有双重功能。

Differential expression of two mRNA species indicates a dual function of peripheral myelin protein PMP22 in cell growth and myelination.

作者信息

Bosse F, Zoidl G, Wilms S, Gillen C P, Kuhn H G, Müller H W

机构信息

Department of Neurology, Heinrich-Heine-University of Düsseldorf, Germany.

出版信息

J Neurosci Res. 1994 Mar 1;37(4):529-37. doi: 10.1002/jnr.490370412.

DOI:10.1002/jnr.490370412
PMID:8021974
Abstract

Two peripheral myelin protein PMP22 transcripts, CD25 and SR13, have been identified by Northern blot and RNA-polymerase chain reaction (PCR) methods in rat. The CD25 and SR13 mRNA species (each approximately 1.8 kb in size) differ significantly in their 5'-untranslated region (5'-UTR) sequences but encode the same protein. While CD25 mRNA is largely confined to the peripheral nervous system, the SR13 transcript is more ubiquitously expressed in rat tissues. Both transcripts are differentially expressed during postnatal sciatic nerve development. While CD25 expression steadily increases from low levels in neonates up to a maximum at postnatal day 14, SR13 mRNA levels are elevated at birth but decrease throughout adulthood. CD25 and SR13 transcripts are expressed at very low constant levels in developing and adult brain. In degenerating and regenerating segments of injured peripheral nerve changes in CD25 mRNA levels clearly resemble the expression pattern of other myelin genes, whereas expression of SR13 is inversely correlated with the time course of Schwann cell proliferation. In cultured rat meningeal fibroblasts SR13 mRNA expression is strictly growth arrest-specific and independent of forskolin. On the other hand, regulation of CD25 mRNA levels in these cells is more complex with respect to interfering effects of serum and forskolin. In cultured Schwann cells neither CD25 nor SR13 expression is growth arrest-specific. However, both transcript levels are consistently enhanced by forskolin under all conditions of cell growth tested. Expression of CD25 (but not SR13) depends on high Schwann cell density. Our results substantiate the hypothesis that PMP22 serves two biological functions, one related to cell growth (SR13) and another to myelination (CD25).

摘要

通过Northern印迹法和RNA聚合酶链反应(PCR)方法,在大鼠中鉴定出了两种外周髓鞘蛋白PMP22转录本,即CD25和SR13。CD25和SR13 mRNA种类(大小均约为1.8 kb)在其5'-非翻译区(5'-UTR)序列上有显著差异,但编码相同的蛋白质。虽然CD25 mRNA主要局限于外周神经系统,但SR13转录本在大鼠组织中表达更为广泛。在出生后坐骨神经发育过程中,这两种转录本的表达存在差异。CD25的表达从新生儿期的低水平稳步增加,在出生后第14天达到最高,而SR13 mRNA水平在出生时升高,但在成年期逐渐下降。CD25和SR13转录本在发育中的和成年大脑中以非常低的恒定水平表达。在受损外周神经的退化和再生节段中,CD25 mRNA水平的变化明显类似于其他髓鞘基因的表达模式,而SR13的表达与雪旺细胞增殖的时间进程呈负相关。在培养的大鼠脑膜成纤维细胞中,SR13 mRNA的表达严格具有生长停滞特异性,且与福斯可林无关。另一方面,这些细胞中CD25 mRNA水平的调节在血清和福斯可林的干扰作用方面更为复杂。在培养的雪旺细胞中,CD25和SR13的表达都不具有生长停滞特异性。然而,在所有测试的细胞生长条件下,福斯可林均能持续增强这两种转录本的水平。CD25(而非SR13)的表达取决于高雪旺细胞密度。我们的结果证实了以下假设:PMP22具有两种生物学功能,一种与细胞生长(SR13)相关,另一种与髓鞘形成(CD25)相关。

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