Calcium signalling during chemotaxis.
The role of Ca2+ in chemotaxis of eosinophils from the newt Taricha granulosa was investigated using fluorescent indicators and digital imaging microscopy. In response to serum chemoattractant, cytoplasmic Ca2+ concentration ([Ca2+]i) rises prior to polarization. In polarized locomoting cells [Ca2+]i gradients (tail-high-front-low) are always seen, and when cells turn [Ca2+]i rises transiently and falls fastest and furthest in the new direction of cell motion. These Ca2+ signals, which are required for polarization and locomotion, arise from Ca2+ derived from internal stores released in response to inositol 1,4,5-trisphosphate (InsP3) (because microinjected heparin fully blocks them). 1,2-Diacyl-sn-glycerol (DAG), which is co-produced with InsP3, has an inhibitory effect on Ca2+ signals, an effect apparently mediated by protein kinase C. Studies with caged InsP3 reveal that InsP3-responsive stores appear to be concentrated in the nuclear and microtubule-organizing centre regions and that InsP3 moves so rapidly within the cell that it is effectively a global secondary messenger. Thus, stable [Ca2+] gradients observed during unidirectional migration appear to result from the concentration of InsP3-responsive Ca2+ stores in the rear of the cell. By contrast, we propose that reorientation of the [Ca2+] gradient prior to a change in direction of motion results from the joint actions of InsP3 and DAG, with InsP3 acting as a global secondary messenger stimulating Ca2+ release and DAG, through protein kinase C, acting as a spatially restricted secondary messenger inhibiting [Ca2+] increases locally near the site of chemotactic stimulation.
Fay
F S
FS
Department of Physiology, University of Massachusetts Medical School, Worcester 01605, USA.
Gilbert
S H
SH
Brundage
R A
RA
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D004804:Eosinophils / Q000502:physiology*; D012455:Salamandridae; D015398:Signal Transduction
D002118:Calcium