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波形蛋白中间丝维持生长中神经突中线粒体的膜电位。

Vimentin Intermediate Filaments Maintain Membrane Potential of Mitochondria in Growing Neurites.

作者信息

Dayal Alexander A, Parfenteva Olga I, Wang Huiying, Gebreselase Blen Amare, Gyoeva Fatima K, Alieva Irina B, Minin Alexander A

机构信息

Institute of Protein Research, Russian Academy of Sciences, 119334 Moscow, Russia.

Belozersky Institute of Physical and Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia.

出版信息

Biology (Basel). 2024 Nov 29;13(12):995. doi: 10.3390/biology13120995.

Abstract

Neural precursor cells contain two types of intermediate filaments (IFs): neurofilaments consisting of three IV type proteins and vimentin belonging to the type III IF proteins that disappear at the later stages of differentiation. The involvement of vimentin in neurogenesis was demonstrated earlier; however, the role of its temporary expression in neurons is not clear. We showed that the vimentin IFs that interacted with mitochondria maintained their membrane potential at the appropriate level, and thus, ensured their proper function. We examined the dependence of the mitochondrial membrane potential on the expression of vimentin in a CAD catecholaminergic neuronal cell line that was actively dividing in full culture media but stopped growing and started developing neurites when the serum was removed. Using the CRISPR Cas9 system to knock out the vimentin gene in these cells, we investigated the impact of this on the mitochondrial membrane potential. Our data show that the deletion of the vimentin IFs led to a decrease in the level of the mitochondrial potential. When the vimentin network in these cells was reconstituted by transfection with a plasmid that encoded human protein, the level of the potential was restored. Interestingly, mutated vimentin with a disrupted mitochondria-binding site had no such effect. Our data point to vimentin as a possible target in some neurological pathologies.

摘要

神经前体细胞含有两种中间丝(IFs):由三种IV型蛋白组成的神经丝和属于III型IF蛋白的波形蛋白,波形蛋白在分化后期消失。波形蛋白在神经发生中的作用早已得到证实;然而,其在神经元中短暂表达的作用尚不清楚。我们发现,与线粒体相互作用的波形蛋白中间丝将其膜电位维持在适当水平,从而确保其正常功能。我们在一种CAD儿茶酚胺能神经元细胞系中研究了线粒体膜电位对波形蛋白表达的依赖性,该细胞系在完全培养基中积极分裂,但当去除血清时停止生长并开始长出神经突。利用CRISPR Cas9系统敲除这些细胞中的波形蛋白基因,我们研究了这对线粒体膜电位的影响。我们的数据表明,波形蛋白中间丝的缺失导致线粒体电位水平下降。当用编码人类蛋白的质粒转染这些细胞来重建波形蛋白网络时,电位水平得以恢复。有趣的是,具有破坏的线粒体结合位点的突变波形蛋白没有这种作用。我们的数据表明波形蛋白可能是某些神经病理学的一个潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d4/11726714/5fc08e2ae8ac/biology-13-00995-g001.jpg

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