Prof. Andreas H. Guse- University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
Abstract
NAADP evoked Calcium Signaling
Nicotinic acid adenine dinucleotide phosphate (NAADP) evokes the initial local Ca2+ signals observed upon T cell activation, termed Ca2+ microdomains1,2. Ca2+ microdomains occur within hundreds of milliseconds up to approx. 15 to 25 s following directed T cell receptor ligation.
In recent years, we have identified the essential proteins involved in Ca2+ microdomain formation, e.g. NAADP forming enzyme DUOX3, NAADP receptor HN1L/JPT24, NAADP dependent ion channels ryanodine receptor 1 (RYR1)1,2], as well as further amplification mechanisms via purinergic receptors P2X4 and P2X75.
Recently, we used novel tools and approaches to investigate further aspects of Ca2+ microdomains. First, we developed MASTER-NAADP, a membrane-permeable precursor of NAADP, to directly initiate NAADP signaling in intact cells6. Secondly, the very close co-localization of RYR1 and ORAI1 suggests that ER-PM junctions are the hub for the first Ca2+ microdomains close to the immune synapse2. Using known quantitative data, we simulated the process of Ca2+ microdomain formation at single ER-PM junctions, and predict localization of RYR1 around the ER cone7. Thirdly, focusing on endo-lysosomal Ca2+ signaling, we employed photothermal heating of plasmonic nanoparticles taken up into endo-lysosomes to initiate Ca2+ signaling from single lysosomes9.
Very recently, the complex regulation of DUOX2 to catalyze NAADP formation in T cells was deciphered9.
Overall, NAADP signaling in T cells represents a fine-tuned signaling system with fascinating properties – both in biochemistry as well as in cell biology.
Bio
Andreas H. Guse studied chemistry, biology and pedagogics at the University of Hamburg, and received his PhD (Dr. rer. nat.) from the Department of Chemistry in 1990. From 1990 to 1993, Andreas was Laboratory Head at the Max-Planck-Society, Clinical Research Groups for Rheumatology, Erlangen, Germany. In 1993 he received his Habilitation in Biochemistry (Dr. med. habil.) at the Friedrich-Alexander-University of Erlangen-Nürnberg, Germany. He established his own laboratory end of 1993 and served as group leader at the Institute of Biochemistry and Molecular Biology I at University Medical Centre Hamburg-Eppendorf (UKE) until 2013. He was appointed Privatdozent in 1994 and Professor in 2000. Since 2013 he is Full Professor and Director of the Department of Biochemistry and Molecular Cell Biology (IBMZ), at UKE. Since 2007 he also serves as Vice-Dean of Education and Students’ Affaires at the Medical Faculty/UKE. He has been speaker of Collaborative Research Center SFB1328 ‘Adenine Nucleotides in Immunity and Inflammation’ (https://www.sfb1328.de) since 2018. Since 2020 he also has served as president of the European Calcium Society (ECS). His laboratory, The Calcium Signalling Group, focuses on intracellular signaling mechanisms, with emphasis on calcium signaling the second messenger nicotinic acid adenine dinucleotide phosphate (NAADP). Within FOR 5705 ‘Neuroflame - Defence and demise of inflamed neurons’ he investigates, together with Marc Freichel (Heidelberg), calcium signaling evoked by the second messenger NAADP downstream of glutamate-mediated excitotoxicity.
