, Volume 6, Issue 3, pp 135–141 | Cite as

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. MarchukEmail author
Original Article


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.


Nocodazole Microtubule Dynamic Hereditary Spastic Paraplegia Microtubule Network Microtubule Depolymerization 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by grant P01 NS26630 to M.P.V. I.K.S. was the recipient of a Ruth K. Broad Biomedical Research Foundation Fellowship Award.


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Ingrid K. Svenson
    • 1
  • Mark T. Kloos
    • 1
  • Amy Jacon
    • 1
  • Carol Gallione
    • 1
  • April C. Horton
    • 2
  • Margaret A. Pericak-Vance
    • 3
  • Michael D. Ehlers
    • 2
  • Douglas A. Marchuk
    • 1
    Email author
  1. 1.Department of Molecular Genetics and MicrobiologyDuke University Medical CenterDurhamUSA
  2. 2.Department of NeurobiologyDuke University Medical CenterDurhamUSA
  3. 3.Department of Medicine, Center for Human GeneticsDuke University Medical CenterDurhamUSA

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