部門公開セミナー

日 時 2012年11月22日 16:00~17:00
場 所 山手3号館 2階 西 大会議室
演 者 Yanzhuang Wang, Ph.D.(Associate Professor, University of Michigan, USA)
演 題 Golgi Biogenesis, Function, and Defects in Diseases
要 旨

Dr. Wang's current research focuses on the biogenesis, function, and defects of the Golgi in diseases. The Golgi apparatus is a membrane-bound organelle that serves as a central conduit for protein and lipid modification, processing, trafficking and secretion. Proteins encoded by over one-third of the genes in the human genome, such as hormones (e.g. insulin), neurotransmitters, growth factors, digestive enzymes, antibodies and extracellular matrix proteins, all go through the Golgi, where they are processed, concentrated, sorted, and transported to the correct location. A unique feature of this membrane organelle is the stack of the flattened cisternae, but the molecular mechanism and biological significance of stack formation remain elusive. Dr. Wang’s research aims to understand how this unique stacked structure is formed, why this structure is important for its function, and how a new Golgi is generated when the cell divides. In particular, Dr. Wang is interested in studying the proteins that help “glue” the cisternae together to form a stack and the role of ubiquitin in regulation of Golgi membrane dynamics during the cell cycle. In the last few years, he and his colleagues have developed a unique multidisciplinary approach employing biochemistry, cell biology, electron microscopy, and more recently proteomics, combined with a novel in vitro reconstitution assay, to provide a mechanistic explanation for Golgi structure formation and function. He found that stack formation directly involves the Golgi stacking proteins GRASP65 and GRASP55, which play complementary and essential roles by forming mitotically regulated trans-oligomers that hold the Golgi membranes into stacks. Using GRASP65/55 as tools to manipulate Golgi stack formation, he demonstrated that Golgi stacking functions as a flux regulator to ensure accurate protein modifications. He also discovered that monoubiquitination of Golgi membrane proteins during mitosis is essential for subsequent membrane fusion and identified HACE1 and VCIP135 as the ubiquitination and deubiquitinating enzymes whose activity is required for post-mitotic Golgi reassembly. Most recently, he has gathered intriguing preliminary data concerning the structural and functional defects of the Golgi in cell culture and mouse models for cancer as well as cardiovascular and Alzheimer’s diseases.

連絡先 大橋 正人(内線5561)