Disease relevance of SPG20

• SPG20 is mutated in Troyer syndrome, an hereditary spastic paraplegia [1].
• Troyer syndrome is an autosomal recessive form of spastic paraplegia caused by a frameshift mutation in the spartin (SPG20) gene [2].

High impact information on SPG20

• Comparative sequence analysis indicates that spartin shares similarity with molecules involved in endosomal trafficking and with spastin, a molecule implicated in microtubule interaction that is commonly mutated in HSP [1].
• We report mapping of the TRS locus to chromosome 13q12.3 and identify a frameshift mutation in SPG20, encoding spartin [1].
• Mutation of spartin (SPG20) underlies a complicated form of hereditary spastic paraplegia, a disorder principally defined by the degeneration of upper motor neurons [3].
• Spartin is also enriched at the centrosome within mitotic structures [3].
• Investigation of these spartin-positive vesicles reveals that a large proportion colocalizes with the synaptic vesicle marker synaptotagmin [3].

Biological context of SPG20

• 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 [2].

Anatomical context of SPG20

• The nuclear expression of spartin closely mirrors that of the snRNP (small nuclear ribonucleoprotein) marker alpha-Sm, a component of the spliceosome [3].
• In undifferentiated non-neuronal cells, spartin displays a nuclear and diffuse cytosolic profile, whereas spartin transiently accumulates in the trans-Golgi network and subsequently decorates discrete puncta along neurites in terminally differentiated neuroblastic cells [3].
• The hereditary spastic paraplegia protein spartin localises to mitochondria [4].
• We observed cytoplasmic expression of spartin in all transfected cell lines [4].
• Using superimposed organelle markers or immunocytochemistry staining, we established that spartin localizes to mitochondria and that this localization is dependent on sequences in the C-terminal region [4].

Other interactions of SPG20

• We also show that spartin recruits AIP4 to lipid droplets and promotes ubiquitination of lipid droplet-associated protein, adipophilin, which regulates turnover of lipid droplets [5].

Analytical, diagnostic and therapeutic context of SPG20

• Multiple sequence alignment has revealed the presence of a sequence domain of approximately 80 amino acids in two molecules, spartin and spastin, mutated in hereditary spastic paraplegia [6].
• Immunocytochemistry staining using anti-alpha-tubulin antibody provided evidence for partial co-localization of spartin with microtubules [4].

References