Organelle selection determines agonist-specific Ca2+ signals in pancreatic acinar and beta cells.
How different extracellular stimuli can evoke different spatiotemporal Ca2+ signals is uncertain. We have elucidated a novel paradigm whereby different agonists use different Ca2+-storing organelles ("organelle selection") to evoke unique responses. Some agonists select the endoplasmic reticulum (ER), and others select lysosome-related (acidic) organelles, evoking spatial Ca2+ responses that mirror the organellar distribution. In pancreatic acinar cells, acetylcholine and bombesin exclusively select the ER Ca2+ store, whereas cholecystokinin additionally recruits a lysosome-related organelle. Similarly, in a pancreatic beta cell line MIN6, acetylcholine selects only the ER, whereas glucose mobilizes Ca2+ from a lysosome-related organelle. We also show that the key to organelle selection is the agonist-specific coupling messenger(s) such that the ER is selected by recruitment of inositol 1,4,5-trisphosphate (or cADP-ribose), whereas lysosome-related organelles are selected by NAADP.
Yamasaki
Michiko
M
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK.
Masgrau
Roser
R
Morgan
Anthony J
AJ
Churchill
Grant C
GC
Patel
Sandip
S
Ashcroft
Stephen J H
SJ
Galione
Antony
A
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001839:Bombesin / Q000378:metabolism; D002118:Calcium / Q000819:agonists / Q000378:metabolism*; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D018942:Macrolides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008954:Models, Biological; D009249:NADP / Q000031:analogs & derivatives / Q000737:chemistry; D015388:Organelles / Q000502:physiology; D010179:Pancreas / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D014466:Ultraviolet Rays
D004791:Enzyme Inhibitors; D018942:Macrolides; C057620:bafilomycin A; D009249:NADP; C024376:NAADP; D019284:Thapsigargin; D000109:Acetylcholine; D001839:Bombesin; D002118:Calcium