title: Activation of syntaxin 1C, an alternative splice variant of HPC-1/syntaxin 1A, by phorbol 12-myristate 13-acetate (PMA) suppresses glucose transport into astroglioma cells via the glucose transporter-1 (GLUT-1).
abstract: Syntaxin 1C is an alternative splice variant lacking the transmembrane domain of HPC-1/syntaxin 1A. We found previously that syntaxin 1C is expressed as a soluble protein in human astroglioma (T98G) cells, and syntaxin 1C expression is enhanced by stimulation with phorbol 12-myristate 13-acetate (PMA). However, the physiological function of syntaxin 1C is not known. In this study, we examined the relationship between syntaxin 1C and glucose transport. First, we discovered that glucose transporter-1 (GLUT-1) was the primary isoform in T98G cells. Second, we demonstrated that glucose uptake in T98G cells was suppressed following an increase in endogenous syntaxin 1C after stimulation with PMA, which did not alter the expression levels of other plasma membrane syntaxins. We further examined glucose uptake and intracellular localization of GLUT-1 in cells that overexpressed exogenous syntaxin 1C; glucose uptake via GLUT-1 was inhibited without affecting sodium-dependent glucose transport. The value of Vmax for the dose-dependent uptake of glucose was reduced in syntaxin 1C-expressing cells, whereas there was no change in Km. Immunofluorescence studies revealed a reduction in the amount of GLUT-1 in the plasma membrane in cells that expressed syntaxin 1C. Based on these results, we postulate that syntaxin 1C regulates glucose transport in astroglioma cells by changing the intracellular trafficking of GLUT-1. This is the first report to indicate that a syntaxin isoform that lacks a transmembrane domain can regulate the intracellular transport of a plasma membrane protein.
authors.affiliation: Department of Physiology, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan. nakayama@kyorin-u.ac.jp
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakayama
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Mikoshiba
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Yamamori
authors.forename: Kimio
authors.initials: K
authors.lastname: Akagawa
mesh_terms: D017398:Alternative Splicing; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D001254:Astrocytoma / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D045744:Cell Line, Tumor; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D006801:Humans; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D050827:Syntaxin 1; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000954:Antigens, Surface; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; C495677:SLC2A1 protein, human; C494212:STX1A protein, human; D050827:Syntaxin 1; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate