Characterization of seipin/BSCL2, a protein associated with spastic paraplegia 17

Neurobiol Dis. 2008 Aug;31(2):266-77. doi: 10.1016/j.nbd.2008.05.004. Epub 2008 May 22.


Seipin, which is encoded by the BSCL2 gene, is a glycoprotein of unknown biochemical function that is associated with dominant hereditary motor neuron diseases. Mutations in the N-glycosylation site of seipin are associated with the disease states and result in accumulation of unfolded protein in the endoplasmic reticulum (ER), leading to the unfolded protein response (UPR) and cell death, suggesting that these diseases are tightly associated with ER stress. Here, we determined the subcellular localization, functional domains, and distribution of seipin in tissues. Our studies show that the transmembrane domains in seipin are critical for ER retention, ubiquitination, formation of inclusions, and activation of UPR. Using immunohistochemistry, seipin expression is detected in neurons in the spinal cord and in the frontal lobe cortex of the brain. The present study provides new insights into the biology of seipin protein that should help our understanding of the pathogenesis of seipin-related diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Central Nervous System / metabolism*
  • Central Nervous System / ultrastructure
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum / ultrastructure
  • GTP-Binding Protein gamma Subunits / analysis
  • GTP-Binding Protein gamma Subunits / genetics
  • GTP-Binding Protein gamma Subunits / metabolism*
  • HeLa Cells
  • Humans
  • Immunohistochemistry
  • Mice
  • Motor Cortex / metabolism
  • Motor Cortex / ultrastructure
  • Motor Neuron Disease / genetics
  • Motor Neuron Disease / metabolism*
  • Motor Neuron Disease / physiopathology
  • Motor Neurons / metabolism*
  • Motor Neurons / ultrastructure
  • Oxidative Stress / physiology
  • Paraplegia / genetics
  • Paraplegia / metabolism*
  • Paraplegia / physiopathology
  • Protein Folding
  • Protein Structure, Tertiary / physiology
  • Spinal Cord / metabolism
  • Spinal Cord / ultrastructure
  • Ubiquitination / physiology


  • BSCL2 protein, human
  • GTP-Binding Protein gamma Subunits