Morphological changes of T cells following formation of the immunological synapse modulate intracellular calcium signals.
Sustained Ca(2+) influx through plasma membrane Ca(2+) released-activated Ca(2+) (CRAC) channels is essential for T cell activation. Since inflowing Ca(2+) inactivates CRAC channels, T cell activation is only possible if Ca(2+)-dependent inactivation is prevented. We have previously reported that sustained Ca(2+) influx through CRAC channels requires both mitochondrial Ca(2+) uptake and mitochondrial translocation towards the plasma membrane in order to prevent Ca(2+)-dependent channel inactivation. Here, we show that morphological changes following formation of the immunological synapse (IS) modulate Ca(2+) influx through CRAC channels. Cell shape changes were dependent on the actin cytoskeleton, and they sustained Ca(2+) entry by bringing mitochondria and the plasma membrane in closer proximity. The increased percentage of mitochondria beneath the plasma membrane following shape changes occurred in all 3 dimensions and correlated with an increase in the amplitude of Ca(2+) signals. The shape change-dependent mitochondrial localization close to the plasma membrane prevented CRAC channel inactivation even in T cells in which dynein motor protein-dependent mitochondria movements towards the plasma membrane were completely abolished, highlighting the importance of the shape change-dependent control of Ca(2+) influx. Our results suggest that morphological changes do not only facilitate an efficient contact with antigen presenting cells but also strongly modulate Ca(2+) dependent T cell activation.
Quintana
Ariel
A
Department of Biophysics, University of Saarland, Homburg, Germany. ptaqgo@uks.eu
Kummerow
Carsten
C
Junker
Christian
C
Becherer
Ute
U
Hoth
Markus
M
D000199:Actins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000276:immunology*; D002462:Cell Membrane / Q000378:metabolism; D048430:Cell Shape; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D054992:Immunological Synapses / Q000276:immunology*; D042541:Intracellular Space / Q000378:metabolism*; D019169:Jurkat Cells; D008928:Mitochondria / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*
D000199:Actins; D015220:Calcium Channels; D002118:Calcium