Seminar

 

▶ Subject : Translational Control of Complex Brain Function

▶ Speaker:  Dr. Joel D. Richter (University of Massachusetts Medical School)

▶ Date :  4:00PM/ Jun. 1(Fri)/2012

▶ Place :  Auditorium(1F), Postech Biotech Center

 

*Abstract
The formation and maintenance of neural circuits in the mammal central nervous system (CNS) require the coordinated expression of genes not just at the transcriptional level, but at the translational level as well. Recent evidence demonstrates that regulated mRNA translation is necessary for certain forms of synaptic plasticity, the cellular basis of learning and memory. In addition, regulated translation helps guide axonal growth cones to their targets on other neurons or at the neuro-muscular junction. Several neurologic syndromes have been correlated with and indeed may be caused by aberrant translation; one important example is the Fragile X Mental Retardation Syndrome. Although translation in the CNS is regulated by multiple mechanisms and factors, I will focus on cytoplasmic  polyadenylation of mRNAs and the proteins that mediate this process. The RNA binding protein CPEB regulates local (that is, synaptodendritic) polyadenylation-induced translation of target mRNAs in neurons. The
poly(A) polymerase Gld2, the deadenylase PARN, and the translational inhibitory factor neuroguidin (Ngd) are identified as components of the polyadenylation apparatus that are critical to CPEB-dependent translation in neurons. Synaptic stimulation promotes CPEB phosphorylation and PARN expulsion from the polyadenylation complex, permitting Gld2-dependent polyadenylation and translation of target mRNAs. shRNA-mediated depletion of Gld2 in vivo attenuates mature synaptic spine number and protein synthesis-dependent longterm potentiation (LTP) in the hippocampus (a part of the brain required for longterm memory storage) whereas depletion of Ngd increases mature spine number and LTP. Moreover, Gld2 stimulates synthesis of the plasticity protein NMDA receptor subunit NR2A in dendrites while Ngd inhibits it. These data demonstrate that Gld2 and Ngd, members of the cytoplasmic polyadenylation apparatus, exert opposing actions on spine morphogenesis, local translation of NR2A mRNA, and plasticity at hippocampal synapses. The involvement of the cytoplasmic polyadenylation apparatus in the Fragile-X Mental Retardation Syndrome will also be discussed.

 

☎ Inquiry : Prof. Jang Sung Key(279-2298)

*This Seminar will be given in English.