title: The Troyer syndrome (SPG20) protein spartin interacts with Eps15.
abstract: The hereditary spastic paraplegias comprise a group of inherited neurological disorders in which the primary manifestation is spastic weakness of the lower extremities. Troyer syndrome is an autosomal recessive form of spastic paraplegia caused by a frameshift mutation in the spartin (SPG20) gene. Currently, neither the localization nor the functions of the spartin protein are known. In this study, we generated anti-spartin antibodies and found that spartin is both cytosolic and membrane-associated. Using a yeast two-hybrid approach, we screened an adult human brain library for binding partners of spartin. We identified Eps15, a protein known to be involved in endocytosis and the control of cell proliferation. This interaction was confirmed by fusion protein "pull-down" experiments as well as a cellular redistribution assay. Our results suggest that spartin might be involved in endocytosis, vesicle trafficking, or mitogenic activity, and that impairment in one of these processes may underlie the long axonopathy in patients with Troyer syndrome.
authors.affiliation: Cellular Neurology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 35, Room 2C-913, 9000 Rockville Pike, Bethesda, MD 20892-3704, USA.
authors.forename: Joanna C
authors.initials: JC
authors.lastname: Bakowska
authors.forename: Russell
authors.initials: R
authors.lastname: Jenkins
authors.forename: James
authors.initials: J
authors.lastname: Pendleton
authors.forename: Craig
authors.initials: C
authors.lastname: Blackstone
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002460:Cell Line; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011506:Proteins / Q000378:metabolism*; D015419:Spastic Paraplegia, Hereditary / Q000378:metabolism*; D013577:Syndrome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C486206:EPS15 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D011506:Proteins; C464787:SPART protein, human