Hypertonia-associated protein Trak1 is a novel regulator of endosome-to-lysosome trafficking

JOURNAL OF MOLECULAR BIOLOGY

卷:382

Article

Webber, Elizabeth¹  Li, Lian¹  Chin, Lih-Shen¹ 

[1] Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30332 USA

关键词: endosome;    Hrs;    Trak1;    trafficking;    hypertonia;   

DOI  :  10.1016/j.jmb.2008.07.045

来源: Elsevier

【 摘 要 】

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. (c) 2008 Elsevier Ltd. All rights reserved.

【 授权许可】

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