Neurobiology of Disease Quantitative and Functional Analyses of Spastin in the Nervous System: Implications for Hereditary Spastic Paraplegia
نویسندگان
چکیده
Joanna M. Solowska,1 Gerardo Morfini,2 Aditi Falnikar,1 B. Timothy Himes,1,3 Scott T. Brady,2 Dongyang Huang,2 and Peter W. Baas1 1Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, 2Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, Illinois 60612, and 3Department of Veterans Affairs Medical Center, Philadelphia, Pennsylvania 19104
منابع مشابه
The Hereditary Spastic Paraplegia Gene, spastin, Regulates Microtubule Stability to Modulate Synaptic Structure and Function
BACKGROUND Hereditary Spastic Paraplegia (HSP) is a devastating neurological disease causing spastic weakness of the lower extremities and eventual axonal degeneration. Over 20 genes have been linked to HSP in humans; however, mutations in one gene, spastin (SPG4), are the cause of >40% of all cases. Spastin is a member of the ATPases associated with diverse cellular activities (AAA) protein fa...
متن کاملThe Drosophila Homologue of the Hereditary Spastic Paraplegia Protein, Spastin, Severs and Disassembles Microtubules
Hereditary spastic paraplegias (HSPs), a group of neurodegenerative disorders characterized by lower-extremity spasticity and weakness, are most commonly caused by mutations in the spastin gene, which encodes a AAA+ ATPase related to the microtubule-severing protein katanin. A Drosophila homolog of spastin (D-spastin) was identified recently, and D-spastin RNAi-treated or genetic null flies sho...
متن کاملMutations of SPG4 are responsible for a loss of function of spastin, an abundant neuronal protein localized in the nucleus.
Mutations of spastin are responsible for the most common autosomal dominant form of hereditary spastic paraplegia (AD-HSP), a disease characterized by axonal degeneration of corticospinal tracts and posterior columns. Generation of polyclonal antibodies specific to spastin has revealed two isoforms of 75 and 80 kDa in both human and mouse tissues with a tissue-specific variability of the isofor...
متن کاملSpastin interacts with the centrosomal protein NA14, and is enriched in the spindle pole, the midbody and the distal axon.
Hereditary spastic paraplegia (HSP) is characterized by the specific retrograde degeneration of the longest axons in the central nervous system, the corticospinal tracts. The gene most frequently involved in autosomal dominant cases of this disease, SPG4, encodes spastin, an ATPase belonging to the AAA family. AAA proteins are thought to exert their function by the energy-dependent rearrangemen...
متن کاملGenetic and chemical modulation of spastin-dependent axon outgrowth in zebrafish embryos indicates a role for impaired microtubule dynamics in hereditary spastic paraplegia.
Mutations in the SPAST (SPG4) gene, which encodes the microtubule-severing protein spastin, are the most common cause of autosomal dominant hereditary spastic paraplegia (HSP). Following on from previous work in our laboratory showing that spastin is required for axon outgrowth, we report here that the related microtubule-severing protein katanin is also required for axon outgrowth in vivo. Usi...
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