Charcot-Marie-Tooth 2B mutations in rab7 cause dosage-dependent neurodegeneration due to partial loss of function

@inproceedings{Cherry2013CharcotMarieTooth2M,
  title={Charcot-Marie-Tooth 2B mutations in rab7 cause dosage-dependent neurodegeneration due to partial loss of function},
  author={Smita Cherry and Eugene Jennifer Jin and Mehmet Neset {\"O}zel and Zhiyuan Lu and Egemen Agi and Dong Wang and Wei-Hung Jung and Daniel C. Epstein and Ian A. Meinertzhagen and Chih-Chiang Chan and Peter Robin Hiesinger},
  booktitle={eLife},
  year={2013}
}
The small GTPase Rab7 is a key regulator of endosomal maturation in eukaryotic cells. Mutations in rab7 are thought to cause the dominant neuropathy Charcot-Marie-Tooth 2B (CMT2B) by a gain-of-function mechanism. Here we show that loss of rab7, but not overexpression of rab7 CMT2B mutants, causes adult-onset neurodegeneration in a Drosophila model. All CMT2B mutant proteins retain 10-50% function based on quantitative imaging, electrophysiology, and rescue experiments in sensory and motor… CONTINUE READING