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.
Experimental Medicine Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Takuya
T
Nishimura
Shin-Ichi
S
Harashima
Hu
H
Yafang
Abner Louis
AL
Notkins
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