Interaction of two hereditary spastic paraplegia gene products, spastin and atlastin, suggests a common pathway for axonal maintenance.
Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder that is characterized by retrograde axonal degeneration that primarily affects long spinal neurons. The disease is clinically heterogeneous, and there are >20 genetic loci identified. Here, we show a physical interaction between spastin and atlastin, two autosomal dominant HSP gene products. Spastin encodes a microtubule (MT)-severing AAA ATPase (ATPase associated with various activities), and atlastin encodes a Golgi-localized integral membrane protein GTPase. Atlastin does not regulate the enzymatic activity of spastin. We also identified a clinical mutation in atlastin outside of the GTPase domain that prevents interaction with spastin in cells. Therefore, we hypothesize that failure of appropriate interaction between these two HSP gene products may be pathogenetically relevant. These data indicate that at least a subset of HSP genes may define a cellular biological pathway that is important in axonal maintenance.
Evans
Katia
K
Department of Pathology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Keller
Christian
C
Pavur
Karen
K
Glasgow
Kristen
K
Conn
Bryan
B
Lauring
Brett
B
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000502:physiology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins; D005799:Genes, Dominant; D018740:Genetic Heterogeneity; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins; D009154:Mutation; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D015419:Spastic Paraplegia, Hereditary / Q000201:enzymology* / Q000235:genetics*; D000074181:Spastin
D008565:Membrane Proteins; C440006:ATL1 protein, human; D000251:Adenosine Triphosphatases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D000074181:Spastin; C400283:SPAST protein, human