title: Recruitment of NAADP-sensitive acidic Ca2+ stores by glutamate.
abstract: NAADP (nicotinic acid-adenine dinucleotide phosphate) is an unusual second messenger thought to mobilize acidic Ca(2+) stores, such as lysosomes or lysosome-like organelles, that are functionally coupled to the ER (endoplasmic reticulum). Although NAADP-sensitive Ca(2+) stores have been described in neurons, the physiological cues that recruit them are not known. Here we show that in both hippocampal neurons and glia, extracellular application of glutamate, in the absence of external Ca(2+), evoked cytosolic Ca(2+) signals that were inhibited by preventing organelle acidification or following osmotic bursting of lysosomes. The sensitivity of both cell types to glutamate correlated well with lysosomal Ca(2+) content. However, interfering with acidic compartments was largely without effect on the Ca(2+) content of the ER or Ca(2+) signals in response to ATP. Glutamate but not ATP elevated cellular NAADP levels. Our results provide evidence for the agonist-specific recruitment of NAADP-sensitive Ca(2+) stores by glutamate. This links the actions of NAADP to a major neurotransmitter in the brain.
authors: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, U.K.
authors: Vinita
authors: V
authors: Pandey
authors: Chia-Chen
authors: CC
authors: Chuang
authors: Alexander M
authors: AM
authors: Lewis
authors: Parvinder K
authors: PK
authors: Aley
authors: Eugen
authors: E
authors: Brailoiu
authors: Nae J
authors: NJ
authors: Dun
authors: Grant C
authors: GC
authors: Churchill
authors: Sandip
authors: S
authors: Patel
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D018698:Glutamic Acid / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D009249:NADP / Q000031:analogs & derivatives* / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
chemical_list: D018698:Glutamic Acid; D009249:NADP; C024376:NAADP; D002118:Calcium