Oncotarget

Research Papers:

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

Takeshi Uemura _, George Tsaprailis and Eugene W. Gerner

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Oncotarget. 2019; 10:5713-5723. https://doi.org/10.18632/oncotarget.27192

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Abstract

Takeshi Uemura1, George Tsaprailis2 and Eugene W. Gerner3

1 Amine Pharma Research Institute, Chuo-ku, Chiba 260-0856, Japan

2 Center for Toxicology, College of Pharmacy, Tucson, Arizona 85721, USA

3 Cancer Prevention Pharmaceuticals, Tucson, Arizona 85718, USA

Correspondence to:

Takeshi Uemura,email: uemura@amine-pharma.com

Keywords: polyamine; caveolin; GSTπ; transport; actin

Received: June 08, 2019     Accepted: August 16, 2019     Published: October 01, 2019

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.


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