Proper long-distance trafficking of membrane-associated cargo is crucial for neuronal health. Recently, RME-8, a protein known for its important role in recycling endocytic cargo in non-neuronal cells from early endosomes to the plasma membrane via the Golgi, was implicated in Parkinson's Disease (PD). A single copy of a specific allele, N855S, in human RME-8 (aka DNAJC13) was closely associated with inherited PD in a particular family, and other rare alleles of human RME-8 have been associated with a related disease, Essential Tremors. Prior to this work RME-8 function had not been studied in neurons, where membrane trafficking pathways are particularly elaborate and specialized. Using C. elegans as a model, our lab has investigated the effects in neurons of perturbing RME-8 function, with a particular emphasis on the effects on endosomes traveling long-distance in neurites. Importantly, in
rme-8(
b1023ts) mutants at restrictive temperature, we find an abnormal accumulation of elongated RAB-5 and RAB-7 positive endosomes in the neurite of ALM mechanosensory neurons. These elongated vesicles are often quite dynamic, but appear to fail in long distance directional movement. We also engineered the homologous PD mutation into the worm via CRISPR (
rme-8 N861S). We observe similar elongated endosomal structures in N861S mutant neurons, but not in young adults, only in aged animals. This appears to mimic PD pathology in that it is strongly associated with aging. Our results point to a key role in endosomal trafficking in the neurite for RME-8, and suggests that failure of such trafficking is important in understanding the etiology of PD.