論文

査読有り
2009年9月

Microtubule-dependent formation of the stigmoid body as a cytoplasmic inclusion distinct from pathological aggresomes

HISTOCHEMISTRY AND CELL BIOLOGY
  • Ryutaro Fujinaga
  • ,
  • Yukio Takeshita
  • ,
  • Kanako Uozumi
  • ,
  • Akie Yanai
  • ,
  • Kazuhiro Yoshioka
  • ,
  • Keiji Kokubu
  • ,
  • Koh Shinoda

132
3
開始ページ
305
終了ページ
318
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1007/s00418-009-0618-9
出版者・発行元
SPRINGER

The stigmoid body (STB) is a neurocytoplasmic inclusion containing huntingtin-associated protein 1 (HAP1), an interactor of huntingtin, and its formation is induced by transfection of HAP1-cDNA into cultured cells. Although STB is believed to play a protective role in polyglutamine diseases, including Huntington's disease and spinal and bulbar muscular atrophy, by sequestering the causative proteins, huntingtin and androgen receptor, respectively, its physiological function and formation remain poorly understood. Therefore, STB is occasionally confused with another cytoplasmic inclusion observed in polyglutamine diseases, the aggresome. Here we examined the subcellular dynamics of STB and compared it immunohistochemically and cytochemically with the aggresome in the rat brain and COS-7 or HeLa cells transfected with HAP1 and/or polyglutamine disease-associated genes. In time-lapse image analysis of HAP1-transfected cells, the HAP1-induced STB is formed from multiple fusions of small HAP1 inclusions characterized by vigorous cytoplasmic movement. In HAP1-transfected cells treated with a microtubule-depolymerizing drug, although the formation of small HAP1 inclusions was not affected, their fusion was critically inhibited. Immunohistochemistry and cytochemistry revealed the absence of association between STB and aggresomal markers, such as ubiquitin/proteasome, intermediate filaments, and the centrosome. Taken together, we concluded that STB is formed by a two-step process comprising microtubule-independent formation of small HAP1 inclusions and microtubule-dependent fusion of these inclusions, and that STB is distinct from pathological aggresomes.

Web of Science ® 被引用回数 : 10

リンク情報
DOI
https://doi.org/10.1007/s00418-009-0618-9
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/19578869
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000269151300006&DestApp=WOS_CPL

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