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

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...

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Bibliographic Details
Published in:Molecular biology of the cell 2007-05, Vol.18 (5), p.1683-1692
Main Authors: Bakowska, Joanna C, Jupille, Henri, Fatheddin, Parvin, Puertollano, Rosa, Blackstone, Craig
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing
Adenosine Triphosphatases - antagonists & inhibitors
Adenosine Triphosphatases - genetics
Adenosine Triphosphatases - metabolism
ATPases Associated with Diverse Cellular Activities
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Base Sequence
Calcium-Binding Proteins - genetics
Calcium-Binding Proteins - metabolism
Cell Line
DNA, Complementary - genetics
Endocytosis
Endosomal Sorting Complexes Required for Transport
Endosomes - metabolism
ErbB Receptors - metabolism
Gene Expression
HeLa Cells
Humans
In Vitro Techniques
Intracellular Signaling Peptides and Proteins - genetics
Intracellular Signaling Peptides and Proteins - metabolism
Luminescent Proteins - genetics
Luminescent Proteins - metabolism
Mutation
Phosphoproteins - genetics
Phosphoproteins - metabolism
Protein Transport
Proteins - antagonists & inhibitors
Proteins - chemistry
Proteins - genetics
Proteins - metabolism
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
RNA, Small Interfering - genetics
Spastic Paraplegia, Hereditary - etiology
Spastic Paraplegia, Hereditary - genetics
Spastic Paraplegia, Hereditary - metabolism
Syndrome
Ubiquitin - metabolism
Vacuolar Proton-Translocating ATPases
Vesicular Transport Proteins - antagonists & inhibitors
Vesicular Transport Proteins - genetics
Vesicular Transport Proteins - metabolism
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Summary: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.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.e06-09-0833