期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 315, 期 1-2, 页码 81-86出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2009.09.023
关键词
IA-2; siRNA; PC12; Dopamine; Hormones; Neurotransmitters
资金
- National Institute of Dental and Craniofacial Research
- National Institutes of Health and in part by a Japan Society for the Promotion of Science Fellowship
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-2 beta 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. Published by Elsevier Ireland Ltd.
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