Endogenous spartin (SPG20) is recruited to endosomes and lipid droplets and interacts with the ubiquitin E3 ligases AIP4 and AIP5

被引:56
作者
Edwards, Thomas L. [1 ,2 ]
Clowes, Virginia E. [1 ,2 ]
Tsang, Hilda T. H. [1 ,2 ]
Connell, James W. [1 ,2 ]
Sanderson, Christopher M. [3 ]
Luzio, J. Paul [1 ,4 ]
Reid, Evan [1 ,2 ]
机构
[1] Univ Cambridge, Addenbrookes Hosp, Cambridge Inst Med Res, Cambridge CB2 0XY, England
[2] Univ Cambridge, Addenbrookes Hosp, Dept Med Genet, Cambridge CB2 0XY, England
[3] Univ Liverpool, Sch Biomed Sci, Physiol Lab, Liverpool L69 3BX, Merseyside, England
[4] Univ Cambridge, Addenbrookes Hosp, Dept Clin Biochem, Cambridge CB2 0XY, England
基金
英国惠康基金;
关键词
epidermal growth factor receptor (EGFR); hereditary spastic paraplegia (HSP); microtubute interacting and trafficking domain; mono-ubiquitination; spartin; HEREDITARY SPASTIC PARAPLEGIA; TROYER-SYNDROME; ESCRT-III; FUNCTIONAL DIVERSITY; PROTEIN SPARTIN; NEDD4; FAMILY; LOCALIZATION; RECOGNITION; DOMAINS; VPS4;
D O I
10.1042/BJ20082398
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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; WWP2 (WW domain-containing E3 ubiquitin protein ligase 2] 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.
引用
收藏
页码:31 / 39
页数:9
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