Linoleic Acid Derivative DCP-LA Stimulates Vesicular Transport of α7 ACh Receptors towards Surface Membrane

Cellular Physiology and Biochemistry

关键词: DCP-LA;    α7 ACh receptor;    Surface expression;    Trafficking;    Protein kinase C;   

DOI  :  10.1159/000339049

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background/Aims We have earlier found that the linoleic acid derivative DCP-LA could ameliorate learning and memory impairment by targeting α7 ACh receptor. The present study aimed at understanding DCP-LA-regulated α7 ACh receptor trafficking. Methods We monitored currents through α7 ACh receptors expressed in Xenopus oocytes and assayed the receptor mobilizations using fractions with a sucrose density gradient centrifugation, synaptosome preparation, and acutely dissociated neurons from rat hippocampal slices. Results DCP-LA persistently potentiated α7 ACh receptor currents, and the effect was inhibited by a protein kinase C (PKC) inhibitor or vesicular transport inhibitors. DCP-LA did not induce PKC phosphorylation of α7 ACh receptors. DCP-LA stimulated translocation of α7 ACh receptors from the cytosol toward the plasma membrane or from extra-synaptosomes into synaptosomes and accumulated the receptors at the presynaptic site in hippocampal neurons. Conclusion The results of the present study demonstrate that DCP-LA increases surface localization of α7 ACh receptors in hippocampal neurons, specifically at presynaptic terminals, by stimulating vesicular transport of the receptors, resulting in potentiation of α7 ACh receptor responses, regardless of PKC phosphorylation of the receptors.

【 授权许可】

CC BY-NC-ND