主题：The ULK/Atg1 Kinase in Development and Disease

报告人：Bo Wang, PhD, Postdoctoral research associate of St Jude Children’s Research Hospital

时间：2018年8月16日（周四），10:00-11:30

地点：北京大学王克桢楼1113会议室

摘要：

Amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and inclusion body myopathy (IBM) are devastating degenerative diseases that primarily affect brain, spinal cord, and skeletal muscle respectively. Affect distinct tissues as they do, ALS/FTD/IBM share common pathological features, namely the presence of ubiquitin+ and TDP-43+ deposits in the disease tissues. Prior studies have identified mutations in genes encoding autophagy-related proteins and RNA-binding proteins in the familial and sporadic ALS/FTD/IBM patients, suggesting possible pathological interplays between the two pathways. Our study focusing on the autophagy-inducing kinases ULK1/2 demonstrated that while ULK1/2 are dispensable for the regulation of constitutive autophagy in the central nervous system, their deficiency in the muscle leads to development of inclusion bodies that highly recapitulated the IBM pathology. In additional to a canonical role in the autophagy regulation, ULK1/2 also have unexpected function in regulating dynamics of RNA binding proteins at least partially by phosphorylating VCP, an AAA ATPase that is found to be frequently mutated in patients with ALS/FTD/IBM phenotype. Future work to further elucidate the underlying mechanisms of how abnormal RNA metabolism contributes to the pathogenesis of ALS/FTD/IBM could facilitate development of effective therapeutic tools for these diseases.

邀请人：饶毅 教授