Interaction of two hereditary spastic paraplegia gene products, spastin and atlastin, suggests a common pathway for axonal maintenance
- 11 July 2006
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 103 (28) , 10666-10671
- https://doi.org/10.1073/pnas.0510863103
Abstract
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.Keywords
This publication has 24 references indexed in Scilit:
- SPG3A protein atlastin-1 is enriched in growth cones and promotes axon elongation during neuronal developmentHuman Molecular Genetics, 2006
- A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNA interferenceNature Genetics, 2003
- Mutations of SPG4 are responsible for a loss of function of spastin, an abundant neuronal protein localized in the nucleusHuman Molecular Genetics, 2003
- SPG3ANeurology, 2002
- A Kinesin Heavy Chain (KIF5A) Mutation in Hereditary Spastic Paraplegia (SPG10)American Journal of Human Genetics, 2002
- Infantile-Onset Ascending Hereditary Spastic Paralysis Is Associated with Mutations in the Alsin GeneAmerican Journal of Human Genetics, 2002
- SPG20 is mutated in Troyer syndrome, an hereditary spastic paraplegiaNature Genetics, 2002
- Hereditary spastic paraplegia: The pace quickensAnnals of Neurology, 2002
- Hereditary Spastic Paraplegia SPG13 Is Associated with a Mutation in the Gene Encoding the Mitochondrial Chaperonin Hsp60American Journal of Human Genetics, 2002
- Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegiaNature Genetics, 1999