ArticleeLife2013
Charcot-Marie-Tooth 2B mutations in rab7 cause dosage-dependent neurodegeneration due to partial loss of function.
Article in eLife, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 80 citations in OpenAlex.
- Article
- Junctions in Jeopardy: the neuromuscular junction is a selective pathological target in Charcot-Marie-Tooth disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Rab4 spatially and functionally converges with Rab7 in the degradative endolysosomal network.Molecular biology of the cell · 2026Article
- Cryo-EM structure of the human MON1A-CCZ1-RAB7A complex provides insights into nucleotide exchange mechanism.Life metabolism · 2025Article
- Shaping and interpretation of Dpp morphogen gradient by endocytic trafficking.PLoS genetics · 2025Article
- Sculpting excitable membranes: voltage-gated ion channel delivery and distribution.Nature reviews. Neuroscience · 2025Review
- Rab7a is an enhancer of TPC2 activity regulating melanoma progression through modulation of the GSK3β/β-Catenin/MITF-axis.Nature communications · 2024Article
- Identification of secretory autophagy as a mechanism modulating activity-induced synaptic remodeling.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Review
- Pan-cellular organelles and suborganelles-from common functions to cellular diversity?Genes & development · 2024Review
- tsCRISPR based identification of Rab proteins required for the recycling ofFrontiers in cell and developmental biology · 2024Article
- Peripheral Neuropathy and Decreased Locomotion of aExperimental neurobiology · 2023Article
- Article
- Receptor Recycling by Retromer.Molecular and cellular biology · 2023Review
- The Osiris family genes function as novel regulators of the tube maturation process in the Drosophila trachea.PLoS genetics · 2023Article
- Mitochondria dysfunction in Charcot Marie Tooth 2B Peripheral Sensory Neuropathy.Communications biology · 2022Article
- Membrane Targeting and GTPase Activity of Rab7 Are Required for Its Ubiquitination by RNF167.International journal of molecular sciences · 2022Article
- Small Rab GTPases in Intracellular Vesicle Trafficking: The Case of Rab3A/Raphillin-3A Complex in the Kidney.International journal of molecular sciences · 2021Review
- Article
- Retromer dysfunction at the nexus of tauopathies.Cell death and differentiation · 2021Review
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11 authors at 3 institutions in 3 countries.
Funding
Abstract
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 neurons in vivo. Consequently, expression of CMT2B mutants at levels between 0.5 and 10-fold their endogenous levels fully rescues the neuropathy-like phenotypes of the rab7 mutant. Live imaging reveals that CMT2B proteins are inefficiently recruited to endosomes, but do not impair endosomal maturation. These findings are not consistent with a gain-of-function mechanism. Instead, they indicate a dosage-dependent sensitivity of neurons to rab7-dependent degradation. Our results suggest a therapeutic approach opposite to the currently proposed reduction of mutant protein function. DOI: http://dx.doi.org/10.7554/eLife.01064.001.
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