轴浆运输
神经退行性变
轴突
神经科学
生物
细胞生物学
疾病
内科学
医学
作者
Shweta Shah,Lucio Schiapparelli,Yuanhui Ma,Satoshi Yokota,Melissa Atkins,Xin Xia,Evan G. Cameron,Thanh Huang,Sarah Saturday,Catalin B Sun,Cara Knasel,Seth Blackshaw,John R. Yates,Hollis T. Cline,Jeffrey L. Goldberg
出处
期刊:eLife
[eLife Sciences Publications, Ltd.]
日期:2022-03-08
卷期号:11
被引量:10
摘要
Many neurons in the adult central nervous system, including retinal ganglion cells (RGCs), degenerate and die after injury. Early axon protein and organelle trafficking failure is a key component in many neurodegenerative disorders yet changes to axoplasmic transport in disease models have not been quantified. We analyzed early changes in the protein ‘transportome’ from RGC somas to their axons after optic nerve injury and identified transport failure of an anterograde motor protein Kif5a early in RGC degeneration. We demonstrated that manipulating Kif5a expression affects anterograde mitochondrial trafficking in RGCs and characterized axon transport in Kif5a knockout mice to identify proteins whose axon localization was Kif5a-dependent. Finally, we found that knockout of Kif5a in RGCs resulted in progressive RGC degeneration in the absence of injury. Together with expression data localizing Kif5a to human RGCs, these data identify Kif5a transport failure as a cause of RGC neurodegeneration and point to a mechanism for future therapeutics.
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