IA-2 modulates dopamine secretion in PC12 cells.
The secretion of the hormone insulin from beta cells is modulated by the expression of the dense core vesicle transmembrane protein IA-2. Since IA-2 is found in neuroendocrine cells throughout the body, the present experiments were initiated to determine whether the expression of IA-2 also modulates the secretion of neurotransmitters. Using the dopamine-secreting pheochromocytoma cell line PC12, we found that the overexpressions of IA-2 increased the cellular content and secretion of dopamine, whereas the knockdown of IA-2 by siRNA decreased the cellular content and secretion of dopamine. Neither the overexpression nor knockdown of IA-2 influenced the uptake of [H(3)]dopamine by PC12 cells, but did influence the amount of [H(3)]dopamine secreted. Overexpression of IA-2 also increased the level of the dense core vesicle-associated proteins Rab3A, IA-2beta and secretogranin II, whereas the knockdown of IA-2 decreased the level of these proteins. We conclude that the expression of IA-2 profoundly influences the function of dense core vesicles and has a broad modulating effect on the cellular content and secretion of both hormones and neurotransmitters.
Nishimura
Takuya
T
Experimental Medicine Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Harashima
Shin-Ichi
S
Yafang
Hu
H
Notkins
Abner Louis
AL
D000818:Animals; D001323:Autoantibodies / Q000235:genetics / Q000378:metabolism*; D002273:Carcinogens / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D022142:Secretory Vesicles / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001323:Autoantibodies; D002273:Carcinogens; C096322:ICA512 autoantibody; D034741:RNA, Small Interfering; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D004298:Dopamine