| First Author | Webber E | Year | 2008 |
| Journal | J Mol Biol | Volume | 382 |
| Issue | 3 | Pages | 638-51 |
| PubMed ID | 18675823 | Mgi Jnum | J:168968 |
| Mgi Id | MGI:4939351 | Doi | 10.1016/j.jmb.2008.07.045 |
| Citation | Webber E, et al. (2008) Hypertonia-associated protein Trak1 is a novel regulator of endosome-to-lysosome trafficking. J Mol Biol 382(3):638-51 |
| abstractText | Hypertonia, which is characterized by stiff gait, abnormal posture, jerky movements, and tremor, is associated with a number of neurological disorders, including cerebral palsy, dystonia, Parkinson's disease, stroke, and spinal cord injury. Recently, a spontaneous mutation in the gene encoding trafficking protein, kinesin-binding 1 (Trak1), was identified as the genetic defect that causes hypertonia in mice. The subcellular localization and biological function of Trak1 remain unclear. Here we report that Trak1 interacts with hepatocyte-growth-factor-regulated tyrosine kinase substrate (Hrs), an essential component of the endosomal sorting and trafficking machinery. Double-label immunofluorescence confocal studies show that the endogenous Trak1 protein partially colocalizes with Hrs on early endosomes. Like Hrs, both overexpression and small-interfering-RNA-mediated knockdown of Trak1 inhibit degradation of internalized epidermal growth factor receptors through a block in endosome-to-lysosome trafficking. Our findings support a role for Trak1 in the regulation of Hrs-mediated endosomal sorting and have important implications for understanding hypertonia associated with neurological disorders. |
