2016
DOI: 10.1007/s00018-016-2274-2
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Roles of extracellular nucleotides and P2 receptors in ectodomain shedding

Abstract: Ectodomain shedding of integral membrane receptors results in the release of soluble molecules and modification of the transmembrane portions to mediate or modulate extracellular and intracellular signalling. Ectodomain shedding is stimulated by a variety of mechanisms, including the activation of P2 receptors by extracellular nucleotides. This review describes in detail the roles of extracellular nucleotides and P2 receptors in the shedding of various cell surface molecules, including amyloid precursor protei… Show more

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Cited by 22 publications
(18 citation statements)
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“…Another important effect seen in many types of cells is blebbing and microvesiculation of the cell surface membrane within seconds to minutes following P2X7 activation (MacKenzie et al ., ; Verhoef et al ., ). Yet another downstream effect of P2X7 activation is the shedding of cell surface L‐selectin (CD62L) and CD23 from immune cells resulting from the stimulated proteolytic activity of ADAM10 and ADAM17 (Gu et al ., ; Pupovac and Sluyter, ). Other pro‐inflammatory effects include rapid secretion of MMP‐9 from monocytes (Gu and Wiley, ), activation of the MAP kinase pathway (Panenka et al ., ) and activation of the key transcriptional factor NF‐κB complex (Ferrari et al ., ; Korcok et al ., ).…”
Section: The P2x7 Receptor Is Best Known For Its Pro‐inflammatory Funmentioning
confidence: 99%
“…Another important effect seen in many types of cells is blebbing and microvesiculation of the cell surface membrane within seconds to minutes following P2X7 activation (MacKenzie et al ., ; Verhoef et al ., ). Yet another downstream effect of P2X7 activation is the shedding of cell surface L‐selectin (CD62L) and CD23 from immune cells resulting from the stimulated proteolytic activity of ADAM10 and ADAM17 (Gu et al ., ; Pupovac and Sluyter, ). Other pro‐inflammatory effects include rapid secretion of MMP‐9 from monocytes (Gu and Wiley, ), activation of the MAP kinase pathway (Panenka et al ., ) and activation of the key transcriptional factor NF‐κB complex (Ferrari et al ., ; Korcok et al ., ).…”
Section: The P2x7 Receptor Is Best Known For Its Pro‐inflammatory Funmentioning
confidence: 99%
“…P2X subunits share similar membrane topology: Intracellular N- and C-termini, two membrane-spanning domains, and an extracellular loop containing an ATP binding site (16,17). P2X7 is involved in various physiological and pathophysiological processes, including activation of the inflammasome and inflammatory factors (18), stimulation of metalloproteases (19), and the generation of reactive oxygen and nitrogen species (20). Previous studies reported that P2X7 may be a susceptibility gene in non-obese diabetic mice (21,22).…”
Section: Introductionmentioning
confidence: 99%
“…Multiple studies have demonstrated secretion of cytokines from the IL-1 family (IL-1b, IL-1a, IL-18) in response to P2X7dependent activation of the NLRP3-caspase-1 inflammasome (Giuliani et al, 2017). Other cytokines such as those relying on cleavage by metalloproteinases (e.g., TNF-a) are also released following P2X7 activation as well as other cell surface proteins (e.g., L-selectin, VCAM-1, CD23, and CD14) which are shed (Pupovac and Sluyter, 2016). The particular cytokines released by P2X7 may depend on the cell type under examination, for example, in T lymphocytes, P2X7 can contribute to IL-2 production and secretion (Yip et al, 2009).…”
Section: P2x7 Receptormentioning
confidence: 99%