Ca²⁺ and calpain control membrane expansion during the rapid cell spreading of neutrophils.
Following adherence of neutrophils to the endothelium, neutrophils undergo a major morphological change that is a necessary prelude to their extravasation. We show here that this shape change is triggered by an elevation of cytosolic inositol (1,4,5)-trisphosphate (IP3), to provoke physiological Ca(2+) influx through a store-operated mechanism. This transition from a spherical to 'flattened' neutrophil morphology is rapid (∼100 seconds) and is accompanied by an apparent rapid expansion of the area of the plasma membrane. However, no new membrane is added into the plasma membrane. Pharmacological inhibition of calpain-activation, which is triggered by Ca(2+) influx during neutrophil spreading, prevents normal cell flattening. In calpain-suppressed cells, an aberrant form of cell spreading can occur where an uncoordinated and localised expansion of the plasma membrane is evident. These data show that rapid neutrophil spreading is triggered by Ca(2+) influx, which causes activation of calpain and release of furled plasma membrane to allow its apparent 'expansion'.
Neutrophil Signalling Group, Institute of Molecular and Experimental Medicine, Schools of Medicine and Dentistry Cardiff University, Heath Park, Cardiff CF14 4XN, UK.
Sharon
S
Dewitt
Robert J
RJ
Francis
Maurice B
MB
Hallett
D000199:Actins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D048430:Cell Shape / Q000502:physiology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D018613:Microscopy, Confocal; D009504:Neutrophils / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D010587:Phagocytosis
D000199:Actins; D015544:Inositol 1,4,5-Trisphosphate; D002154:Calpain; D002118:Calcium
Ca2+ signalling; Cell spreading; IP3; Inositol (1,4,5)-trisphosphate; Neutrophils; Phagocytosis