Spartin Protein Associates with Phospholipids Via Its Plant-Related Senescence Domain and Functions as a Lipid Transfer Protein

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Shaw, Maureen Ashlee
Neuroscience and Neurobiology
thesis / dissertation description
Troyer syndrome is a hereditary spastic paraplegia caused by a mutation that leads to a complete loss of expression of spartin protein. The plant-related senescence domain in spartin is highly conserved and present in over 150 proteins, but its function is unknown. Our results indicate that spartin associates with phospholipids via its senescence domain.Phospholipids are important components of intracellular membranes and play roles in many cellular processes. Knock-down of spartin results in impaired cell division. The phospholipid phosphatidylinositol 3-phosphate (PI3P) is present at midbodies, where it recruits proteins for cytokinesis. Our findings demonstrate that spartin colocalizes with PI3P at midbodies, and knock-down of spartin results in fewer cells with PI3P at midbodies.Lipid transfer proteins shuttle lipids between intracellular membranes. Our data suggest that spartin functions as a novel lipid transfer protein. The pathophysiology of Troyer syndrome may be due to defective maintenance and transport of phospholipids between membranes.