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

Daisuke Ito, Taishi Fujisawa, Hiroshi Iida, Norihiro Suzuki

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)266-277
Number of pages12
JournalNeurobiology of Disease
Volume31
Issue number2
DOIs
Publication statusPublished - 2008 Aug 1

Keywords

  • BSCL2
  • Endoplasmic reticulum stress
  • Lipodystrophy
  • Motor neuron disease
  • Seipin
  • Unfolded protein response

ASJC Scopus subject areas

  • Neurology

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