d1 dopamine receptor signaling is modulated by the r7 rgs protein eat-16 and the r7 binding protein rsbp-1 in caenoerhabditis elegans motor neurons多巴胺d1受体信号调制的r7该蛋白质吃16个和r7绑定蛋白rsbp-1 caenoerhabditis线虫运动神经元.pdf

D1 Dopamine Receptor Signaling Is Modulated by the R7 RGS Protein EAT-16 and the R7 Binding Protein RSBP-1 in Caenoerhabditis elegans Motor Neurons 2 1 1 1 2 Khursheed A. Wani , Mary Catanese , Robyn Normantowicz , Muriel Herd , Kathryn N. Maher , Daniel L. Chase1,2* 1 Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, Massachusetts, United States of America, 2 Molecular and Cellular Biology Program, University of Massachusetts, Amherst, Massachusetts, United States of America Abstract Dopamine signaling modulates voluntary movement and reward-driven behaviors by acting through G protein-coupled receptors in striatal neurons, and defects in dopamine signaling underlie Parkinson’s disease and drug addiction. Despite the importance of understanding how dopamine modifies the activity of striatal neurons to control basal ganglia output, the molecular mechanisms that control dopamine signaling remain largely unclear. Dopamine signaling also controls locomotion behavior in Caenorhabditis elegans. To better understand how dopamine acts in the brain we performed a large- scale dsRNA interference screen in C. elegans for genes required for endogenous dopamine signaling and identified six genes (eat-16, rsbp-1, unc-43, flp-1, grk-1, and cat-1) required for dopamine-mediated behavior. We then used a combination of mutant analysis and cell-specific transgenic rescue experiments to investigate the functional interaction between the proteins encoded by two of these genes, eat-16 and rsbp-1, within single cell types and to examine their role in the modulation of dopamine receptor signaling. We found that EAT-16 and RSBP-1 act together to m