Oral Presentation Australasia Extracellular Vesicles Conference 2017

Elucidating the Mechanism and Function of Apoptotic Cell Disassembly for Drug Targeting (#3)

Georgia K Atkin-Smith 1 , Rochelle Tixeira 1 , Lanzhou Jiang 1 , Stephanie Paone 1 , Sarah Caruso 1 , Amy A Baxter 1 , Mark D Hulett 1 , Erika Duan 1 , Weisan Chen 1 , Ivan Poon 1
  1. La Trobe University, Melbourne, VICTORIA, Australia

Apoptosis (programmed cell death) occurs in essentially all tissues as part of development, homeostasis, and pathogenic processes including chronic inflammation and infection. During apoptosis, dying cells can disassemble into smaller membrane-bound vesicles called apoptotic bodies, a process that could facilitate efficient removal of apoptotic material to maintain tissue homeostasis. Under certain pathological conditions, cellular materials such as cytokines, cell surface molecules and microRNA can be packaged into apoptotic bodies as a mechanism to regulate immunity and tissue repair. Since billions of cells undergo apoptosis daily, the importance of apoptotic cell disassembly and clearance for health and disease is fundamental, yet the mechanisms involved in the formation of apoptotic bodies are poorly understood. These mechanisms also represent attractive targets for the development of novel therapeutics. Here, we describe a new mechanism of cell disassembly by apoptotic cells via the formation of a novel membrane protrusion called apoptopodia. Mechanistically, we have identified pannexin 1 membrane channels as a key regulator of apoptotic cell disassembly. Functionally, the formation of apoptotic bodies via apoptopodia could play an important role in influenza A virus infection by trafficking viral proteins and infectious viral particles. Additionally, we have also identified a novel selection of drugs that can modulate apoptotic body formation. Understanding the mechanistic basis of this process will generate fundamental knowledge of the downstream consequence of cell death.