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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2006-07, Vol.103 (28), p.10666-10671
Main Authors: Evans, Katia, Keller, Christian, Pavur, Karen, Glasgow, Kristen, Conn, Bryan, Lauring, Brett
Format: Article
Language:English
Subjects:
Adenosine triphosphatases
Adenosine Triphosphatases - genetics
Adenosine Triphosphatases - metabolism
Amino acids
Animals
Antibodies
Axons - physiology
Biological Sciences
Cellular biology
Cercopithecus aethiops
COS Cells
Gene loci
Genes, Dominant
Genetic disorders
Genetic engineering
Genetic Heterogeneity
Genetic mutation
Goods and services tax
GTP Phosphohydrolases - genetics
GTP Phosphohydrolases - metabolism
GTP-Binding Proteins
HeLa Cells
Humans
Membrane Proteins
Mutation
Plasmids
Signal Transduction - genetics
Signal Transduction - physiology
Small interfering RNA
Spastic Paraplegia, Hereditary - enzymology
Spastic Paraplegia, Hereditary - genetics
Spastin
Studies
Transfection
Yeasts
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0510863103