报告题目：Neuronal Development & CDKL5-related Disorders
报告人：熊志奇，中国科学院神经科学研究所研究员兼课题组长
主持人：李晓涛 教授
报告时间：3月21日 14:00（周四）
报告地点：闵行生科院534报告厅
报告人简介：熊志奇博士，1992年本科毕业于四川大学华西药学院（原华西医科大学）药学系，1995年获得中国科学院上海药物研究所神经药理学硕士，2000年获得美国贝勒医学院药理和神经科学博士学位，博士毕业后在美国杜克大学神经生物学系做博士后研究，2003年8月起担任美国杜克大学神经生物学系兼职助理教授，同年回国任中国科学院神经科学研究所研究员兼课题组长，2003年入选中国科学院“百人计划”。
报告摘要：The X-link gene cyclin-dependent kinase-like 5 (CDKL5) is mutated in patients with severe neurodevelopmental disorders including an early-onset variant of Rett syndrome. The expression of CDKL5 is developmentally regulated and enriched in the brain. Our recent studies have shown that CDKL5 plays important roles in neuronal development such as neurite growth and dendritic spine morphogenesis. Polarized protein trafficking is fundamental to neuronal development and function. Palmitoylation, a reversible lipid modification, has emerged as an important mechanism for regulating this process. Palmitoylated proteins are sorted in the secretory pathways and trafficked to specific compartments. Although no evidence exists, it is possible that in secretory organelles some non-palmitoylated proteins may achieve polarized trafficking by association with palmitoylated proteins. The postsynaptic scaffolding protein PSD-95 is a major palmitoylated protein in neurons and its synaptic targeting depends on palmitoylation4. We find that PSD-95 interacts with CDKL5, a protein whose mutations cause severe neurodevelopmental disorders, in a palmitoylation-dependent fashion and regulates its targeting to excitatory synapses. Interestingly, certain disease-associated mutations which abolish this interaction reduce synaptic localization of CDKL5. Moreover, disruption of this interaction diminishes synaptic targeting of CDKL5 and inhibits dendritic spine growth. Thus, our findings reveal an unexpected role of palmitoylated PSD-95 in synaptic targeting of CDKL5, which may represent a novel mechanism for protein trafficking. These results may also provide insights into the pathogenesis of CDKL5-related disorders.
