GSTΠ stimulates caveolin-1-regulated polyamine uptake via actin remodeling

Takeshi Uemura, George Tsaprailis, Eugene W. Gerner

Research output: Contribution to journalArticle

Abstract

Polyamines spermidine and spermine, and their diamine precursor putrescine, are essential for normal cellular functions in both pro- and eukaryotes. Cellular polyamine levels are regulated by biosynthesis, degradation and transport. Transport of dietary and luminal bacterial polyamines in gastrointestinal (GI) tissues plays a significant role in tissue polyamine homeostasis. We have reported that caveolin-1 play an inhibitory role in polyamine uptake in GI tissues. We investigated the mechanism of caveolin-1-regulated polyamine transport. We found that glutathione S-transferase Π(GSTΠ) was secreted from caveolin-1 knockdown cells and stimulated spermidine transport in human colon-derived HCT116 cells. GSTΠ secreted in the medium increased S-glutathionylated protein level in the plasma membrane fraction. Proteomic analysis revealed that actin was S-glutathionylated by GSTΠ. Immunofluorescence microscopy demonstrated that actin filaments around plasma membrane were S-glutathionylated in caveolin-1 knockdown cells. Inhibition of actin remodeling by jasplakinolide caused a decrease in polyamine uptake activity. These data support a model in which caveolin-1 negatively regulates polyamine uptake by inhibiting GSTΠ secretion, which stimulates actin remodeling and endocytosis.

Original languageEnglish (US)
Pages (from-to)5713-5723
Number of pages11
JournalOncotarget
Volume10
Issue number55
StatePublished - Jan 1 2019

Fingerprint

Caveolin 1
Polyamines
Glutathione Transferase
Actins
jasplakinolide
Spermidine
Cell Membrane
HCT116 Cells
Diamines
Putrescine
Spermine
Protein S
Endocytosis
Eukaryota
Actin Cytoskeleton
Fluorescence Microscopy
Proteomics
Colon
Homeostasis

Keywords

  • Actin
  • Caveolin
  • GSTπ
  • Polyamine
  • Transport

ASJC Scopus subject areas

  • Oncology

Cite this

GSTΠ stimulates caveolin-1-regulated polyamine uptake via actin remodeling. / Uemura, Takeshi; Tsaprailis, George; Gerner, Eugene W.

In: Oncotarget, Vol. 10, No. 55, 01.01.2019, p. 5713-5723.

Research output: Contribution to journalArticle

Uemura, Takeshi ; Tsaprailis, George ; Gerner, Eugene W. / GSTΠ stimulates caveolin-1-regulated polyamine uptake via actin remodeling. In: Oncotarget. 2019 ; Vol. 10, No. 55. pp. 5713-5723.
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