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Bao, Y; Ledderose, C; Graf, AF; Brix, B; Birsak, T; Lee, A; Zhang, J; Junger, WG.
mTOR and differential activation of mitochondria orchestrate neutrophil chemotaxis.
J Cell Biol. 2015; 210(7):1153-1164 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Brix Bianca
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Number of Figures: 9
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Abstract:
Neutrophils use chemotaxis to locate invading bacteria. Adenosine triphosphate (ATP) release and autocrine purinergic signaling via P2Y2 receptors at the front and A2a receptors at the back of cells regulate chemotaxis. Here, we examined the intracellular mechanisms that control these opposing signaling mechanisms. We found that mitochondria deliver ATP that stimulates P2Y2 receptors in response to chemotactic cues, and that P2Y2 receptors promote mTOR signaling, which augments mitochondrial activity near the front of cells. Blocking mTOR signaling with rapamycin or PP242 or mitochondrial ATP production (e.g., with CCCP) reduced mitochondrial Ca(2+) uptake and membrane potential, and impaired cellular ATP release and neutrophil chemotaxis. Autocrine stimulation of A2a receptors causes cyclic adenosine monophosphate accumulation at the back of cells, which inhibits mTOR signaling and mitochondrial activity, resulting in uropod retraction. We conclude that mitochondrial, purinergic, and mTOR signaling regulates neutrophil chemotaxis and may be a pharmacological target in inflammatory diseases. © 2015 Bao et al.
Find related publications in this database (using NLM MeSH Indexing)
Adenosine Triphosphate - genetics
Adenosine Triphosphate - metabolism
Animals -
Chemotaxis - drug effects
Chemotaxis - physiology
HL-60 Cells -
Humans -
Indoles - pharmacology
Membrane Potential, Mitochondrial - drug effects
Membrane Potential, Mitochondrial - physiology
Mice -
Mitochondria - genetics
Mitochondria - metabolism
Neutrophil Activation - drug effects
Neutrophil Activation - physiology
Neutrophils - cytology
Neutrophils - metabolism
Purines - pharmacology
Receptors, Purinergic P2Y2 - genetics
Receptors, Purinergic P2Y2 - metabolism
Signal Transduction - drug effects
Signal Transduction - physiology
Sirolimus - pharmacology
TOR Serine-Threonine Kinases - antagonists & inhibitors
TOR Serine-Threonine Kinases - genetics
TOR Serine-Threonine Kinases - metabolism

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