Spastin Binds to Lipid Droplets and Affects Lipid Metabolism

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Hereditary spastic paraplegia (HSP) is a genetically heterogeneous neurological disease characterized by weakness and spasticity of the lower limbs, caused by progressive retrograde degeneration of the corticospinal axons, the longest in the central nervous system. The most commonly mutated gene in autosomal dominant forms of HSP, SPAST, encodes for spastin, a microtubule-severing protein. Spastin has been implicated in several processes involving remodeling of membrane structures. We now show that the longest spastin form, spastin-M1, harbors a lipid droplet targeting sequence, which allows targeting of the protein to the surface of lipid droplets, the organelles where cells store neutral lipids. Furthermore, we demonstrate that depletion of the homologous spastin proteins in both flies and worms affects lipid droplet number and triacylglycerol content. Our study adds to recent discoveries that implicate other HSP proteins in lipid droplet and lipid metabolism, and strongly suggests that lipid droplet dysfunction in neurons should be investigated to understand pathogenesis of HSP.

Vyšlo v časopise: Spastin Binds to Lipid Droplets and Affects Lipid Metabolism. PLoS Genet 11(4): e32767. doi:10.1371/journal.pgen.1005149
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005149

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