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2015-05-27 神经生物学前沿学术报告 Weimin Hong

 

报告题目:Regulatory mechanisms of dopamine transporter

报告人:  Weimin Hong Ph.D.

Assistant Professor

College of Pharmacy and Health Sciences

Butler University

Indianapolis, IN, US

时间:   2015年05月28日(周四),下午:14:00-15:00

地点:   西区生物楼329会议室

主办单位:中国科学院脑功能与脑疾病重点实验室

中国科学技术大学生命科学学院

报告简介:

The dopamine transporter (DAT) clears the extracellular dopamine released during neurotransmission and is a major target for both therapeutic and addictive psychostimulant amphetamines. By monitoring surface-labeled DAT in transfected dopamine neurons from embryonic rat mesencephalic cultures, we find that PKC activation induces DAT ubiquitination and lysosomal degradation. In contrast, quantitative assessment of DAT recycling reveals that DAT returns to the surface of dopamine neurons after internalization by amphetamine. The distinct sorting pathways of DAT suggest differential regulation of dopamine signaling during neurotransmission.

 

As DAT is an integral membrane protein that resides within a complex lipid milieu, we also explored novel modulatory mechanisms of membrane lipids on DAT function. Membrane cholesterol addition increased DAT binding Bmax values for cocaine analogs, without altering cell surface DAT levels. Using substituted cysteine scanning method, we also identified multiple residues located on TM1, TM6, TM7, and TM12 of DAT that are sensitive to alterations in the membrane cholesterol content. Our findings support the hypothesis that DAT adopts an outward facing conformation in a cholesterol-rich membrane environment.

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