Troyer Syndrome Protein Spartin Is Mono-Ubiquitinated and Functions in EGF Receptor Trafficking
| Autor: | Henri J. Jupille, Craig Blackstone, Joanna C. Bakowska, Parvin Fatheddin, Rosa Puertollano |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Vacuolar Proton-Translocating ATPases
Small interfering RNA DNA Complementary Endosome Recombinant Fusion Proteins media_common.quotation_subject Vesicular Transport Proteins Gene Expression Cell Cycle Proteins Endosomes In Vitro Techniques Endocytosis medicine.disease_cause Cell Line Bacterial Proteins Ubiquitin medicine Humans Epidermal growth factor receptor RNA Small Interfering Internalization Molecular Biology Adaptor Proteins Signal Transducing media_common Adenosine Triphosphatases Mutation Base Sequence Endosomal Sorting Complexes Required for Transport biology Spastic Paraplegia Hereditary Calcium-Binding Proteins Intracellular Signaling Peptides and Proteins Proteins Syndrome Articles Cell Biology Phosphoproteins Transport protein ErbB Receptors Luminescent Proteins Protein Transport Cancer research biology.protein ATPases Associated with Diverse Cellular Activities HeLa Cells |
| Zdroj: | Molecular Biology of the Cell. 18:1683-1692 |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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