Association of CHMP4B and autophagy with micronuclei: implications for cataract formation.

Association of CHMP4B and autophagy with micronuclei: implications for cataract formation.
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DOI:
10.1155/2014/974393
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发表时间:
2014
影响因子:
--
通讯作者:
Stenmark H
Stenmark H
中科院分区:
生物学3区
文献类型:
--
作者:
Sagona AP;Nezis IP;Stenmark H

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自噬是细胞自我降解的一种机制,对细胞的稳态和分化具有重要作用。转运所需的内体分选复合物(ESCRT)机制的组分是内体分选以及自噬和胞质分裂完成所需的。在这里,我们表明,ESCRT-III亚基CHMP 4 B不仅定位于正常的细胞动力学桥,而且染色体桥和微核,后者周围的溶酶体和自噬体。此外,CHMP 4 B可以与染色质共免疫沉淀。有趣的是,与常染色体显性后极性白内障相关的CHMP 4 B突变消除了CHMP 4 B定位于微核的能力。我们认为CHMP 4 B通过与染色质的结合,可能参与了微核和其他单核染色质的自噬溶酶体降解。这可能对透镜细胞分化过程中的DNA降解有影响,从而潜在地保护透镜细胞免于白内障发展。
Autophagy is a mechanism of cellular self-degradation that is very important for cellular homeostasis and differentiation. Components of the endosomal sorting complex required for transport (ESCRT) machinery are required for endosomal sorting and also for autophagy and the completion of cytokinesis. Here we show that the ESCRT-III subunit CHMP4B not only localizes to normal cytokinetic bridges but also to chromosome bridges and micronuclei, the latter surrounded by lysosomes and autophagosomes. Moreover, CHMP4B can be co-immunoprecipitated with chromatin. Interestingly, a CHMP4B mutation associated with autosomal dominant posterior polar cataract abolishes the ability of CHMP4B to localize to micronuclei. We propose that CHMP4B, through its association with chromatin, may participate in the autophagolysosomal degradation of micronuclei and other extranuclear chromatin. This may have implications for DNA degradation during lens cell differentiation, thus potentially protecting lens cells from cataract development.
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