title: Cytoskeleton rotation relocates mitochondria to the immunological synapse and increases calcium signals.
abstract: Ca2+microdomains and spatially resolved Ca2+signals are highly relevant for cell function. In T cells, local Ca2+signaling at the immunological synapse (IS) is required for downstream effector functions. We present experimental evidence that the relocation of the MTOC towards the IS during polarization drags mitochondria along with the microtubule network. From time-lapse fluorescence microscopy we conclude that mitochondria rotate together with the cytoskeleton towards the IS. We hypothesize that this movement of mitochondria towards the IS together with their functionality of absorption and spatial redistribution of Ca2+is sufficient to significantly increase the cytosolic Ca2+concentration. To test this hypothesis we developed a whole cell model for Ca2+homoeostasis involving specific geometries for mitochondria and use the model to calculate the spatial distribution of Ca2+concentrations within the cell body as a function of the rotation angle and the distance from the IS. We find that an inhomogeneous distribution of PMCA pumps on the cell membrane, in particular an accumulation of PMCA at the IS, increases the global Ca2+concentration and decreases the local Ca2+concentration at the IS with decreasing distance of the MTOC from the IS. Unexpectedly, a change of CRAC/Orai activity is not required to explain the observed Ca2+changes. We conclude that rotation-driven relocation of the MTOC towards the IS together with an accumulation of PMCA pumps at the IS are sufficient to control the observed Ca2+dynamics in T-cells during polarization.
authors.affiliation: Theoretical Physics, Saarland University, 66041 Saarbrücken, Germany.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Maccari
authors.affiliation: Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, 66421 Homburg, Germany.
authors.forename: Renping
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Theoretical Physics, Saarland University, 66041 Saarbrücken, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Peglow
authors.affiliation: Theoretical Physics, Saarland University, 66041 Saarbrücken, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Schwarz
authors.affiliation: Theoretical Physics, Saarland University, 66041 Saarbrücken, Germany.
authors.forename: Ivan
authors.initials: I
authors.lastname: Hornak
authors.affiliation: Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, 66421 Homburg, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Pasche
authors.affiliation: Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, 66421 Homburg, Germany.
authors.forename: Ariel
authors.initials: A
authors.lastname: Quintana
authors.affiliation: Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, 66421 Homburg, Germany. Electronic address: markus.hoth@uks.eu.
authors.forename: Markus
authors.initials: M
authors.lastname: Hoth
authors.affiliation: Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, 66421 Homburg, Germany.
authors.forename: Bin
authors.initials: B
authors.lastname: Qu
authors.affiliation: Theoretical Physics, Saarland University, 66041 Saarbrücken, Germany. Electronic address: h.rieger@mx.uni-saarland.de.
authors.forename: Heiko
authors.initials: H
authors.lastname: Rieger
mesh_terms: D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000276:immunology; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism*; D006801:Humans; D054992:Immunological Synapses / Q000378:metabolism*; D019169:Jurkat Cells; D008928:Mitochondria / Q000378:metabolism*; D012399:Rotation
chemical_list: D002118:Calcium
keywords: CRAC channels; Immunological synapse (IS); Mitochondria; Orai channels; Plasma membrane calcium ATPase (PMCA); Rotation model