{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Bao Y"],"funding":["NIAID NIH HHS","NIGMS NIH HHS"],"pagination":["1153-64"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4586745"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["210(7)"],"pubmed_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."],"journal":["The Journal of cell biology"],"pubmed_title":["mTOR and differential activation of mitochondria orchestrate neutrophil chemotaxis."],"pmcid":["PMC4586745"],"funding_grant_id":["R01 AI080582","R29 GM051477","GM51477","R01 AI072287","T32 GM103702","GM103702","AI080582","R01 GM051477","R01 GM060475","R01 GM116162","GM60475"],"pubmed_authors":["Birsak T","Ledderose C","Lee A","Zhang J","Bao Y","Brix B","Junger WG","Graf AF"],"additional_accession":[]},"is_claimable":false,"name":"mTOR and differential activation of mitochondria orchestrate neutrophil chemotaxis.","description":"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.","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015 Sep","modification":"2024-11-10T08:34:38.376Z","creation":"2019-03-27T01:59:10Z"},"accession":"S-EPMC4586745","cross_references":{"pubmed":["26416965"],"doi":["10.1083/jcb.201503066"]}}