Lysosome-sarcoplasmic reticulum junctions. A trigger zone for calcium signaling by nicotinic acid adenine dinucleotide phosphate and endothelin-1.
Previous studies on pulmonary arterial smooth muscle cells have shown that nicotinic acid adenine dinucleotide phosphate (NAADP) evokes highly localized intracellular Ca(2+) signals by mobilizing thapsigargin-insensitive stores. Such localized Ca(2+) signals may initiate global Ca(2+) waves and contraction of the myocytes through the recruitment of ryanodine receptors on the sarcoplasmic reticulum via Ca(2+)-induced Ca(2+) release. Here we show that NAADP evokes localized Ca(2+) signals by mobilizing a bafilomycin A1-sensitive, lysosome-related Ca(2+) store. These lysosomal stores facilitate this process by co-localizing with a portion of the sarcoplasmic reticulum expressing ryanodine receptors to comprise a highly specialized trigger zone for NAADP-dependent Ca(2+) signaling by the vasoconstrictor hormone, endothelin-1. These findings further advance our understanding of how the spatial organization of discrete, organellar Ca(2+) stores may underpin the generation of differential Ca(2+) signaling patterns by different Ca(2+)-mobilizing messengers.
Division of Biomedical Sciences, School of Biology, Bute Building, University of St. Andrews, St. Andrews, Fife KY16 9TS, UK.
Nicholas P
NP
Kinnear
Francois-Xavier
FX
Boittin
Justyn M
JM
Thomas
Antony
A
Galione
A Mark
AM
Evans
D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D019332:Endothelin-1 / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D008247:Lysosomes / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D018942:Macrolides / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000648:ultrastructure; D009249:NADP / Q000494:pharmacology*; D011651:Pulmonary Artery; D051381:Rats; D017208:Rats, Wistar; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000032:analysis; D012519:Sarcoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D015398:Signal Transduction / Q000187:drug effects*; D019284:Thapsigargin / Q000494:pharmacology; D019108:Tight Junctions / Q000737:chemistry / Q000502:physiology*; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D018942:Macrolides; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D009249:NADP; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; C040929:bafilomycin A1; D025262:Vacuolar Proton-Translocating ATPases; D002118:Calcium