Subcellular localization of spastin: Implications for the pathogenesis of hereditary spastic paraplegia

Ingrid K. Svenson, Mark T. Kloos, Amy Jacon, Carol Gallione, April C. Horton, Margaret A. Pericak-Vance, Michael D. Ehlers, Douglas A. Marchuk

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous diseases characterized by neuronal degeneration that is maximal at the distal ends of the longest axons of the central nervous system. The most common cause of autosomal dominant HSP is mutation of a novel gene encoding spastin, a protein whose function is still being elucidated. One clue concerning spastin function is its intracellular localization. Here, we describe a novel anti-spastin antiserum designed to a unique epitope contained within all splicing isoforms. The antiserum exhibits specific immunostaining of recombinant spastin in intact, fixed cells. Using this reagent, we find that endogenous spastin is located at the centrosome in a variety of cell types at all points in the cell cycle. This localization is resistant to microtubule disruption, suggesting that spastin may be an integral centrosomal protein. In addition to the centrosome, spastin also localizes at discrete focal regions along the axons of primary cultured neurons. These data lend additional support to the emerging hypothesis that spastin plays a role in microtubule dynamics, with a crucial role in microtubule organization.

Original languageEnglish (US)
Pages (from-to)135-141
Number of pages7
JournalNeurogenetics
Volume6
Issue number3
DOIs
StatePublished - Sep 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Cellular and Molecular Neuroscience

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    Svenson, I. K., Kloos, M. T., Jacon, A., Gallione, C., Horton, A. C., Pericak-Vance, M. A., Ehlers, M. D., & Marchuk, D. A. (2005). Subcellular localization of spastin: Implications for the pathogenesis of hereditary spastic paraplegia. Neurogenetics, 6(3), 135-141. https://doi.org/10.1007/s10048-005-0219-2