Motor and Sensory Deficits in the Mice Result from Mutation of the ESCRT Component HGS

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Endocytic trafficking involves the internalization, endosomal sorting and lysosomal degradation of cell surface cargo. Many factors involved in endosomal sorting in mammalian cells have been identified, and mutations in these components are associated with a variety of neurological disorders. While the function of endosomal sorting components has been intensely studied in immortalized cell lines, it is not known what role these factors play in endosomal sorting in the nervous system. In this study, we show that the teetering (tn) gene encodes the hepatocyte growth factor regulated tyrosine kinase substrate (Hgs), a core component of the endosomal sorting pathway. The tn mice exhibit several signs of motor neuron disease, including reduced muscle mass, muscle weakness and motor abnormalities. Although HGS is predicted to be required for the lysosomal degradation of receptor tyrosine kinases, there was no change in the levels of receptor tyrosine kinases in the spinal cords of the tn mice. Instead, we found that HGS is required for synaptic transmission at the neuromuscular junction and for the proper myelination of the peripheral nervous system.

Vyšlo v časopise: Motor and Sensory Deficits in the Mice Result from Mutation of the ESCRT Component HGS. PLoS Genet 11(6): e32767. doi:10.1371/journal.pgen.1005290
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005290

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