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.
Highlights
Polyamines, spermidine and spermine, and their precursor putrescine are essential factors for normal cellular functions [1]
We investigated the mechanism of caveolin-1-regulated polyamine uptake
We found that www.oncotarget.com culture medium of caveolin-1 knockdown cells contained glutathione S-transferase π (GSTπ) and increased Vmax for spermidine uptake without changing Km values (Table 1)
Summary
Polyamines, spermidine and spermine, and their precursor putrescine are essential factors for normal cellular functions [1]. Polyamines can bind to anions such as DNA, RNA and ATP, and regulate their functions [2]. Recent studies demonstrated that polyamines enhanced the synthesis of several proteins at the level of translation [3,4,5]. Polyamines are required for posttranslational modification of eukaryotic translation initiation factor 5A (eIF5A), which is implicated in translation elongation and termination [6]. Polyamines are required for normal cellular functions, high concentrations of polyamines are toxic to cells [7]. The cellular polyamine levels are tightly regulated by biosynthesis, degradation and transport. The transport plays important roles in polyamine homeostasis in addition to de novo synthesis and degradation systems [8]. The major sources of exogenous polyamines come from diet and luminal bacteria [9]
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