Subcellular localization of spastin: implications for the pathogenesis of hereditary spastic paraplegia.

Journal Article (Journal 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.

Full Text

Duke Authors

Cited Authors

  • Svenson, IK; Kloos, MT; Jacon, A; Gallione, C; Horton, AC; Pericak-Vance, MA; Ehlers, MD; Marchuk, DA

Published Date

  • September 2005

Published In

Volume / Issue

  • 6 / 3

Start / End Page

  • 135 - 141

PubMed ID

  • 15891913

International Standard Serial Number (ISSN)

  • 1364-6745

Digital Object Identifier (DOI)

  • 10.1007/s10048-005-0219-2


  • eng

Conference Location

  • United States