Cellular distribution and subcellular localization of spatacsin and spastizin, two proteins involved in hereditary spastic paraplegia

Mol Cell Neurosci. 2011 Jul;47(3):191-202. doi: 10.1016/j.mcn.2011.04.004. Epub 2011 Apr 27.

Abstract

Truncating mutations in the SPG11 and SPG15 genes cause complicated spastic paraplegia, severe neurological conditions due to loss of the functions of spatacsin and spastizin, respectively. We developed specific polyclonal anti-spatacsin (SPG11) and anti-spastizin (SPG15) antisera, which we then used to explore the intracellular and tissue localizations of these proteins. We observed expression of both proteins in human and rat central nervous system, which was particularly strong in cortical and spinal motor neurons as well as in retina. Both proteins were also expressed ubiquitously and strongly in embryos. In cultured cells, these two proteins had similar diffuse punctate, cytoplasmic and sometimes nuclear (spastizin) distributions. They partially co-localized with multiple organelles, particularly with protein-trafficking vesicles, endoplasmic reticulum and microtubules. Spastizin was also found at the mitochondria surface. This first study of the endogenous expression of spatacsin and spastizin shows similarities in their expression patterns that could account for their overlapping clinical phenotypes and involvement in a common protein complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Cells, Cultured
  • Cytoplasm / genetics
  • Cytoplasm / metabolism*
  • Humans
  • Mice
  • Motor Neurons / metabolism*
  • Proteins / genetics
  • Proteins / metabolism*
  • Rats
  • Spastic Paraplegia, Hereditary / genetics
  • Spastic Paraplegia, Hereditary / metabolism

Substances

  • Carrier Proteins
  • Proteins
  • SPG11 protein, human
  • ZFYVE26 protein, human