Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
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
Doi: 10.1083/jcb.201503066
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- Steuber Bianca
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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