TY - JOUR TI - Quantitative transportomics identifies Kif5a as a major regulator of neurodegeneration AU - Shah, Sahil H AU - Schiapparelli, Lucio M AU - Ma, Yuanhui AU - Yokota, Satoshi AU - Atkins, Melissa AU - Xia, Xin AU - Cameron, Evan G AU - Huang, Thanh AU - Saturday, Sarah AU - Sun, Catalina B AU - Knasel, Cara AU - Blackshaw, Seth AU - Yates, John R AU - Cline, Hollis T AU - Goldberg, Jeffrey L A2 - Bovolenta, Paola A2 - Westbrook, Gary L A2 - He, Zhigang A2 - Steen, Judith A VL - 11 PY - 2022 DA - 2022/03/08 SP - e68148 C1 - eLife 2022;11:e68148 DO - 10.7554/eLife.68148 UR - https://doi.org/10.7554/eLife.68148 AB - 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. KW - optic nerve KW - regeneration KW - degeneration KW - retinal ganglion cell KW - proteomics JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -