Skip to Main content Skip to Navigation
Journal articles

A mutation of spastin is responsible for swellings and impairment of transport in a region of axon characterized by changes in microtubule composition.

Abstract : Mutations of the spastin gene (Sp) are responsible for the most frequent autosomal dominant form of spastic paraplegia, a disease characterized by the degeneration of corticospinal tracts. We show that a deletion in the mouse Sp gene, generating a premature stop codon, is responsible for progressive axonal degeneration, restricted to the central nervous system, leading to a late and mild motor defect. The degenerative process is characterized by focal axonal swellings, associated with abnormal accumulation of organelles and cytoskeletal components. In culture, mutant cortical neurons showed normal viability and neurite density. However, they develop neurite swellings associated with focal impairment of retrograde transport. These defects occur near the growth cone, in a region characterized by the transition between stable microtubules rich in detyrosinated alpha-tubulin and dynamic microtubules composed almost exclusively of tyrosinated alpha-tubulin. Here, we show that the Sp mutation has a major impact on neurite maintenance and transport both in vivo and in vitro. These results highlight the link between spastin and microtubule dynamics in axons, but not in other neuronal compartments. In addition, it is the first description of a human neurodegenerative disease which involves this specialized region of the axon.
Complete list of metadatas

Cited literature [45 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-00380098
Contributor : Annie Andrieux <>
Submitted on : Wednesday, May 6, 2009 - 10:34:00 AM
Last modification on : Thursday, September 24, 2020 - 6:30:07 PM
Long-term archiving on: : Thursday, June 10, 2010 - 7:01:53 PM

File

3544.pdf
Publisher files allowed on an open archive

Identifiers

Citation

Anne Tarrade, Coralie Fassier, Sabrina Courageot, Delphine Charvin, Jérémie Vitte, et al.. A mutation of spastin is responsible for swellings and impairment of transport in a region of axon characterized by changes in microtubule composition.. Human Molecular Genetics, Oxford University Press (OUP), 2006, 15 (24), pp.3544-58. ⟨10.1093/hmg/ddl431⟩. ⟨inserm-00380098⟩

Share

Metrics

Record views

2098

Files downloads

1086