uev-1 is an ubiquitin-conjugating enzyme variant that regulates glutamate receptor trafficking in c. elegans neuronsuev-1 ubiquitin-conjugating酶变异,调节谷氨酸受体贩卖秀丽隐杆线虫神经元.pdfVIP

UEV-1 Is an Ubiquitin-Conjugating Enzyme Variant That Regulates Glutamate Receptor Trafficking in C. elegans Neurons 1,4 2 3,4 1 1 Lawrence B. Kramer , Jaegal Shim , Michelle L. Previtera , Nora R. Isack , Ming-Chih Lee , Bonnie L. 3 1 Firestein , Christopher Rongo * 1The Waksman Institute, Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, New Jersey, United States of America, 2 Cancer Experimental Resources Branch, National Cancer Center, Goyang, Korea, 3 Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, New Jersey, United States of America, 4 Graduate Program in Molecular Biosciences, Rutgers, The State University of New Jersey, Piscataway, New Jersey, United States of America Abstract The regulation of AMPA-type glutamate receptor (AMPAR) membrane trafficking is a key mechanism by which neurons regulate synaptic strength and plasticity. AMPAR trafficking is modulated through a combination of receptor phosphorylation, ubiquitination, endocytosis, and recycling, yet the factors that mediate these processes are just beginning to be uncovered. Here we identify the ubiquitin-conjugating enzyme variant UEV-1 as a regulator of AMPAR trafficking in vivo. We identified mutations in uev-1 in a genetic screen for mutants with altered trafficking of the AMPAR subunit GLR-1 in C. elegans interneurons. Loss of uev-1 activity results in the accumulation of GLR-1 in elongated accretions in neuron cell bodies and along the ventral cord neurites. Mutants also have a corresponding behavioral defect—a decrease i