PMP22 accumulation in aggresomes: Implications for CMT1A pathology
PMP22 accumulation in aggresomes: Implications for CMT1A pathology
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DOI：
10.1006/nbdi.1999.0274
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发表时间：
1999-10-01
影响因子：
6.1
通讯作者：
Shooter, EM
中科院分区：
文献类型：
--
作者：
Notterpek, L;Ryan, MC;Shooter, EM
外周髓磷脂蛋白22（Peripheral myelin protein 22，PMP 22）是一种分子量为22 kDa的糖蛋白，主要由雪旺细胞（Schwann cells，SC）表达。PMP22基因位点的重复或缺失与遗传性周围神经病变相关，表明正确的PMP22蛋白水平对SC功能至关重要。以前我们报道过，在SC中，大多数（80%）新合成的PMP 22迅速降解，可能是由于折叠效率低下。在这里，我们表明，抑制蛋白酶体途径的结果在一个显着的积累PMP 22在核周细胞质。用抗遍在蛋白抗体和各种细胞器标记物进行的双重免疫标记表明，积累的PMP 22存在于独特的细胞内内含物（称为侵袭体）中。此外，PMP22在SC中的过表达可诱导蛋白质的核周积聚。总之，这些研究表明，蛋白酶体途径是至关重要的PMP22蛋白水平的调节，并提高了侵略者可能参与PMP22相关的周围神经病变的发病机制的可能性。(C)北京：科学出版社.
Peripheral myelin protein 22 (PMP22) is a 22-kDa glycoprotein mainly expressed by Schwann cells (SCs). Duplication or deletion of the PMP22 gene locus is associated with heritable peripheral neuropathies suggesting that the correct level of PMP22 protein is essential for SC functioning. Previously we reported that in SCs the majority (80%) Of newly synthesized PMP22 is rapidly degraded, possibly due to inefficient folding. Here we show that inhibition of the proteasome pathway results in a marked accumulation of PMP22 in the perinuclear cytoplasm. Double immunolabeling with an anti-ubiquitin antibody and various organelle markers indicates that the accumulated PMP22 is found in unique intracellular inclusions, called aggresomes. Moreover, overexpression of PMP22 in SCs can induce perinuclear accumulation of the protein. Together, these studies suggest that the proteasome pathway is critical for the regulation of PMP22 protein levels and raise the possibility that aggresomes may be involved in the pathogenesis of PMP22-associated peripheral neuropathies. (C) 1999 Academic Press.