Session 2
13 April 2021
4:30 - 6:00pm SGT
5:30 - 7:00pm JST
13 April 2021
4:30 - 6:00pm SGT
5:30 - 7:00pm JST
On-demand viewing is a privilege of SRSS & JSID members and paid registrants.
Abstract
The stratum corneum (SC), the outermost layer of the epidermis, serve as a barrier against the external environment. It consists of dead anucleated keratinocytes functioning as a barrier. The exact molecular mechanisms by which the top layer of living keratinocytes (SG1 cells) die has been largely unknown. To perform single cell biological analysis of SG1-to-SC transition, we combined various fluorescent probes and generated a new system to dissect cell death in SG1 cells, in vivo and in vitro. We demonstrated via intravital imaging procedures that SG1 cells die after prolonged intracellular Ca2+ elevation at neutral pH (phase I). Subsequently, irreversibly sustained rapid intracellular acidification occurs (phase II). In cultured primary SG1 cells, phase I was accompanied by increased cell membrane permeability, an indicator of cell death in general, whereas phase II was essential for disappearance of keratohyalin granules and nuclear DNA. These approaches and findings provide an important framework to understand the molecular mechanisms of the unique cell death pathway in keratinocytes, termed corneoptosis.
The stratum corneum (SC), the outermost layer of the epidermis, serve as a barrier against the external environment. It consists of dead anucleated keratinocytes functioning as a barrier. The exact molecular mechanisms by which the top layer of living keratinocytes (SG1 cells) die has been largely unknown. To perform single cell biological analysis of SG1-to-SC transition, we combined various fluorescent probes and generated a new system to dissect cell death in SG1 cells, in vivo and in vitro. We demonstrated via intravital imaging procedures that SG1 cells die after prolonged intracellular Ca2+ elevation at neutral pH (phase I). Subsequently, irreversibly sustained rapid intracellular acidification occurs (phase II). In cultured primary SG1 cells, phase I was accompanied by increased cell membrane permeability, an indicator of cell death in general, whereas phase II was essential for disappearance of keratohyalin granules and nuclear DNA. These approaches and findings provide an important framework to understand the molecular mechanisms of the unique cell death pathway in keratinocytes, termed corneoptosis.
Bio
Dr. Takeshi Matsui has been a Deputy Team Leader in Dr. Masayuki Amagai’s laboratory at RIKEN-IMS for the past 7 years. He has 20 years of research experience in epidermal differentiation, especially the cornification process, in both academia and industry.
Dr. Takeshi Matsui has been a Deputy Team Leader in Dr. Masayuki Amagai’s laboratory at RIKEN-IMS for the past 7 years. He has 20 years of research experience in epidermal differentiation, especially the cornification process, in both academia and industry.
Abstract
A ligand is located, at long last! Members of the Nod-like receptor (NLR) family act as intracellular sensors of infection. Once they recognize pathogen-associated molecular patterns, they assemble into signalling complexes called inflammasomes, which induce proinflammatory cytokines and pyroptotic cell death. Although rodent NLR family pyrin domain containing 1 (NLRP1) can recognize bacterial toxins and protozoan pathogens, the ligands for human NLRP1 have remained elusive. Robinson et al. found that human NLRP1 senses and is activated by enteroviruses. During human rhinovirus (HRV) infection, the HRV 3C protease cleaves an autoinhibitory N-terminal fragment from NLRP1, which is subsequently degraded. The NLRP1 C-terminal fragment that is released then initiates inflammasome formation. This work offers insights into immune sensing of respiratory viral infections and provides an example of the N-terminal glycine degron pathway in human innate immunity.
A ligand is located, at long last! Members of the Nod-like receptor (NLR) family act as intracellular sensors of infection. Once they recognize pathogen-associated molecular patterns, they assemble into signalling complexes called inflammasomes, which induce proinflammatory cytokines and pyroptotic cell death. Although rodent NLR family pyrin domain containing 1 (NLRP1) can recognize bacterial toxins and protozoan pathogens, the ligands for human NLRP1 have remained elusive. Robinson et al. found that human NLRP1 senses and is activated by enteroviruses. During human rhinovirus (HRV) infection, the HRV 3C protease cleaves an autoinhibitory N-terminal fragment from NLRP1, which is subsequently degraded. The NLRP1 C-terminal fragment that is released then initiates inflammasome formation. This work offers insights into immune sensing of respiratory viral infections and provides an example of the N-terminal glycine degron pathway in human innate immunity.
Bio
Senior research fellow with 10+ years’ experience in epithelial research and for the last 2 years operating in the unique area of epithelial innate immunity.
Senior research fellow with 10+ years’ experience in epithelial research and for the last 2 years operating in the unique area of epithelial innate immunity.
Chairs
Daisuke Nanba, Tokyo Medical and Dental University, Japan
Oliver Dreesen, SRIS, Singapore
Daisuke Nanba, Tokyo Medical and Dental University, Japan
Oliver Dreesen, SRIS, Singapore