Troyer syndrome protein spartin is mono-ubiquitinated and functions in EGF receptor trafficking.

Mol Biol Cell 2007 May 1;18(5):1683-92. Epub 2007 Mar 1.

Cellular Neurology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.

Troyer syndrome is an autosomal recessive hereditary spastic paraplegia caused by mutation in the spartin (SPG20) gene, which encodes a widely expressed protein of unknown function. This mutation results in premature protein truncation and thus might signify a loss-of-function disease mechanism. In this study, we have found that spartin is mono-ubiquitinated and functions in degradation of the epidermal growth factor receptor (EGFR). Upon EGF stimulation, spartin translocates from the cytoplasm to the plasma membrane and colocalizes with internalized EGF-Alexa. Knockdown of spartin by small interfering RNA decreases the rate of EGFR degradation and also affects EGFR internalization, recycling, or both. Furthermore, overexpression of spartin results in a prominent decrease in EGFR degradation. Taken together, our data suggest that spartin is involved in the intracellular trafficking of EGFR and that impaired endocytosis may underlie the pathogenesis of Troyer syndrome.

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http://dx.doi.org/10.1091/mbc.e06-09-0833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1855030PMC
May 2007
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References

(Supplied by CrossRef)

Babst M. et al.
Dev. Cell 2002

Babst M. et al.
EMBO J 1998

Bache K. G. et al.
J. Biol. Chem 2003

Bakowska J. C. et al.
Biochem. Biophys. Res. Commun 2005

Benmerah A. et al.
J. Cell Sci 1999

Benmerah A. et al.
J. Cell Biol 1998

Bishop N. et al.
J. Cell Biol 2002

Carbone R. et al.
Cancer Res 1997

Carter R. E. et al.
J. Biol. Chem 1998

Chen H. et al.
J. Biol. Chem 1999

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