title: Calcium microdomains at the immunological synapse: how ORAI channels, mitochondria and calcium pumps generate local calcium signals for efficient T-cell activation.
abstract: Cell polarization enables restriction of signalling into microdomains. Polarization of lymphocytes following formation of a mature immunological synapse (IS) is essential for calcium-dependent T-cell activation. Here, we analyse calcium microdomains at the IS with total internal reflection fluorescence microscopy. We find that the subplasmalemmal calcium signal following IS formation is sufficiently low to prevent calcium-dependent inactivation of ORAI channels. This is achieved by localizing mitochondria close to ORAI channels. Furthermore, we find that plasma membrane calcium ATPases (PMCAs) are re-distributed into areas beneath mitochondria, which prevented PMCA up-modulation and decreased calcium export locally. This nano-scale distribution-only induced following IS formation-maximizes the efficiency of calcium influx through ORAI channels while it decreases calcium clearance by PMCA, resulting in a more sustained NFAT activity and subsequent activation of T cells.
authors.affiliation: Department of Biophysics, Saarland University, Homburg, Germany. quintana@liai.org
authors.forename: Ariel
authors.initials: A
authors.lastname: Quintana
authors.forename: Mathias
authors.initials: M
authors.lastname: Pasche
authors.forename: Christian
authors.initials: C
authors.lastname: Junker
authors.forename: Dalia
authors.initials: D
authors.lastname: Al-Ansary
authors.forename: Heiko
authors.initials: H
authors.lastname: Rieger
authors.forename: Carsten
authors.initials: C
authors.lastname: Kummerow
authors.forename: Lucia
authors.initials: L
authors.lastname: Nuñez
authors.forename: Carlos
authors.initials: C
authors.lastname: Villalobos
authors.forename: Paul
authors.initials: P
authors.lastname: Meraner
authors.forename: Ute
authors.initials: U
authors.lastname: Becherer
authors.forename: Jens
authors.initials: J
authors.lastname: Rettig
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Niemeyer
authors.forename: Markus
authors.initials: M
authors.lastname: Hoth
mesh_terms: D002118:Calcium / Q000737:chemistry*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D002462:Cell Membrane / Q000201:enzymology; D003599:Cytoskeleton / Q000378:metabolism; D004594:Electrophysiology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D054992:Immunological Synapses; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008856:Microscopy, Fluorescence / Q000379:methods; D008928:Mitochondria / Q000378:metabolism; D000071740:ORAI1 Protein; D017434:Protein Structure, Tertiary; D013601:T-Lymphocytes / Q000166:cytology*
chemical_list: D015220:Calcium Channels; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D049452:Green Fluorescent Proteins; D002118:Calcium