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SHR Neuro Krebs Kardio Lipid

Deak, AT; Groschner, LN; Alam, MR; Seles, E; Bondarenko, AI; Graier, WF; Malli, R.
The endocannabinoid N-arachidonoyl glycine (NAGly) inhibits store-operated Ca2+ entry by preventing STIM1-Orai1 interaction.
J Cell Sci. 2013; 126(Pt 4):879-888 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Alam Muhammad Rizwan
Bondarenko Oleksandr
Deak Andras Tamas
Graier Wolfgang
Groschner Lukas
Malli Roland
Seles Elisabeth
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Number of Figures: 4
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Abstract:
The endocannabiniod anandamide (AEA) and its derivate N-arachidonoyl glycine (NAGly) have a broad spectrum of physiological effects, which are induced by both binding to receptors and receptor-independent modulations of ion channels and transporters. The impact of AEA and NAGly on store-operated Ca(2+) entry (SOCE), a ubiquitous Ca(2+) entry pathway regulating many cellular functions, is unknown. Here we show that NAGly, but not AEA reversibly hinders SOCE in a time- and concentration-dependent manner. The inhibitory effect of NAGly on SOCE was found in the human endothelial cell line EA.hy926, the rat pancreatic β-cell line INS-1 832/13, and the rat basophilic leukemia cell line RBL-2H3. NAGly diminished SOCE independently from the mode of Ca(2+) depletion of the endoplasmic reticulum, whereas it had no effect on Ca(2+) entry through L-type voltage-gated Ca(2+) channels. Enhanced Ca(2+) entry was effectively hampered by NAGly in cells overexpressing the key molecular constituents of SOCE, stromal interacting molecule 1 (STIM1) and the pore-forming subunit of SOCE channels, Orai1. Fluorescence microscopy revealed that NAGly did not affect STIM1 oligomerization, STIM1 clustering, or the colocalization of STIM1 with Orai1, which were induced by Ca(2+) depletion of the endoplasmic reticulum. In contrast, independently from its slow depolarizing effect on mitochondria, NAGly instantly and strongly diminished the interaction of STIM1 with Orai1, indicating that NAGly inhibits SOCE primarily by uncoupling STIM1 from Orai1. In summary, our findings revealed the STIM1-Orai1-mediated SOCE machinery as a molecular target of NAGly, which might have many implications in cell physiology.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Arachidonic Acids - pharmacology
Calcium - metabolism
Calcium Channels - metabolism
Cell Line -
Cell Line, Tumor -
Endocannabinoids - pharmacology
Endothelial Cells - drug effects
Glycine - analogs & derivatives
Humans -
Hydrogen-Ion Concentration -
Membrane Potential, Mitochondrial - drug effects
Membrane Proteins - metabolism
Microscopy, Fluorescence -
Neoplasm Proteins - metabolism
Protein Binding - drug effects
Rats -

Find related publications in this database (Keywords)
Anandamide
Calcium imaging
Endocannabinoids
Endothelial cells
Fluorescent proteins
Fluorescence microscopy
FRET
Fura-2
INS-1 cells
NAGly
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