Intracellular trafficking proteins involved in CMT neuropathy (WP4856)

Charcot-Marie-Tooth (CMT) disease is one of the most common inherited peripheral neuropathies. This peripheral neuropathy is highly heterogeneous (clinically and genetically) and is characterized by a slowly progressive degeneration of the muscle of the foot, lower leg, hand and forearm, accompanied by sensory loss in the toes, fingers and limbs. Mutations in genes involved in intracellular trafficking are increasingly being implicated in various human diseases, including neuronal diseases. This pathway highlights genes with known mutations in CMTs relevant to intracellular trafficking. DNM2 regulates vesicle budding. KIF1B controls vesicle motility on microtubules. LITAF and LRSAM are present in the endocytic pathway and probably regulate protein degradation. Myotubularin-related proteins (MTMR2 and MTMR13) and FIG4 regulate PI metabolism at the level of early endosomes and late endosomes, respectively. Rab7 is present on late endosomes and regulates transport to lysosomes. SH3TC2 regulates endosomal recycling together with Rab11, while NDRG1 regulates membrane traffic at the level of early endosomes together with Rab4 and PRA1. HSPs regulate proteasomal degradation and associate with neurofilaments and actin filaments. FGD4 associates with and regulates actin filaments. MFN2 and GDAP regulate mitochondrial dynamics and mitochondrial axonal transport. This pathway is based on figure 4 and table 1 from [http://europepmc.org/article/PMC/3514635 Bucci et al]. Description adapted from the figure legend and abstract.
last edited

Authors

Kristina Hanspers

Cited In

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Organism

Homo sapiens

Communities

Diseases

Annotations

Pathway Ontology: cellular trafficking cycle pathway

Disease Ontology: Charcot-Marie-Tooth disease nervous system disease genetic disease

Participants

Label Type Compact Identifier
RAB11A GeneProduct ensembl:ENSG00000103769
NDRG1 GeneProduct ensembl:ENSG00000104419
RAB4A GeneProduct ensembl:ENSG00000168118
EGR2 GeneProduct ensembl:ENSG00000122877
PMP22 GeneProduct ensembl:ENSG00000109099
SH3TC2 GeneProduct ensembl:ENSG00000169247
LITAF GeneProduct ensembl:ENSG00000189067
MTMR2 GeneProduct ensembl:ENSG00000087053
DNM2 GeneProduct ensembl:ENSG00000079805
MPZ GeneProduct ensembl:ENSG00000158887
RAB4B GeneProduct ensembl:ENSG00000167578
RAB11B GeneProduct ensembl:ENSG00000185236
LITAF GeneProduct ensembl:ENSG00000189067
RAB25 GeneProduct ensembl:ENSG00000132698
SBF2 GeneProduct ensembl:ENSG00000133812
FIG4 GeneProduct ensembl:ENSG00000112367
MTMR2 GeneProduct ensembl:ENSG00000087053
NEFL GeneProduct ensembl:ENSG00000277586
HSPB1 GeneProduct ensembl:ENSG00000106211
RAB3A GeneProduct ensembl:ENSG00000105649
FGD4 GeneProduct ensembl:ENSG00000139132
HSPB8 GeneProduct ensembl:ENSG00000152137
GDAP1 GeneProduct ensembl:ENSG00000104381
MFN2 GeneProduct ensembl:ENSG00000116688
KIF1B GeneProduct ensembl:ENSG00000054523
LRSAM1 GeneProduct ensembl:ENSG00000148356
FIG4 GeneProduct ensembl:ENSG00000112367
RAB7A GeneProduct ensembl:ENSG00000075785
RAB3B GeneProduct ensembl:ENSG00000169213
MTMR2 GeneProduct ensembl:ENSG00000087053
HSPB1 GeneProduct ensembl:ENSG00000106211
RAB3A GeneProduct ensembl:ENSG00000105649
RAB3B GeneProduct ensembl:ENSG00000169213
SBF2 GeneProduct ensembl:ENSG00000133812
SBF2 GeneProduct ensembl:ENSG00000133812
RABAC1 GeneProduct ensembl:ENSG00000105404
RABAC1 GeneProduct ensembl:ENSG00000105404

References

  1. Bucci C, Bakke O, Progida C. Charcot-Marie-Tooth disease and intracellular traffic. Prog Neurobiol. 2012 Dec;99(3):191–225. PubMed Europe PMC Scholia