title: Endogenous spartin (SPG20) is recruited to endosomes and lipid droplets and interacts with the ubiquitin E3 ligases AIP4 and AIP5.
abstract: The HSPs (hereditary spastic paraplegias) are genetic conditions in which there is distal degeneration of the longest axons of the corticospinal tract, resulting in spastic paralysis of the legs. The gene encoding spartin is mutated in Troyer syndrome, an HSP in which paralysis is accompanied by additional clinical features. There has been controversy over the subcellular distribution of spartin. We show here that, at steady state, endogenous spartin exists in a cytosolic pool that can be recruited to endosomes and to lipid droplets. Cytosolic endogenous spartin is mono-ubiquitinated and we demonstrate that it interacts via a PPXY motif with the ubiquitin E3 ligases AIP4 [atrophin-interacting protein 4; ITCH (itchy E3 ubiquitin protein ligase homologue] [corrected] and AIP5 (WWP1). Surprisingly, the PPXY motif, AIP4 and AIP5 are not required for spartin's ubiquitination, and so we propose that spartin acts as an adaptor for these proteins. Our results suggest that spartin is involved in diverse cellular functions, which may be of relevance to the complex phenotype seen in Troyer syndrome.
authors: University of Liverpool, UK.
authors: Thomas L
authors: TL
authors: Edwards
authors: Virginia E
authors: VE
authors: Clowes
authors: Hilda T H
authors: HT
authors: Tsang
authors: James W
authors: JW
authors: Connell
authors: Christopher M
authors: CM
authors: Sanderson
authors: J Paul
authors: JP
authors: Luzio
authors: Evan
authors: E
authors: Reid
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins; D011992:Endosomes / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology; D008081:Liposomes / Q000378:metabolism; D051379:Mice; D016716:PC12 Cells; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D012097:Repressor Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D018797:Cell Cycle Proteins; D008081:Liposomes; D011506:Proteins; D012097:Repressor Proteins; C464787:SPART protein, human; C432966:ITCH protein, human; C471642:WWP1 protein, human; D044767:Ubiquitin-Protein Ligases