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- Title
Pannexin 1 channels mediate 'find-me' signal release and membrane permeability during apoptosis.
- Authors
Chekeni, Faraaz B.; Elliott, Michael R.; Sandilos, Joanna K.; Walk, Scott F.; Kinchen, Jason M.; Lazarowski, Eduardo R.; Armstrong, Allison J.; Penuela, Silvia; Laird, Dale W.; Salvesen, Guy S.; Isakson, Brant E.; Bayliss, Douglas A.; Ravichandran, Kodi S.
- Abstract
Apoptotic cells release 'find-me' signals at the earliest stages of death to recruit phagocytes. The nucleotides ATP and UTP represent one class of find-me signals, but their mechanism of release is not known. Here, we identify the plasma membrane channel pannexin 1 (PANX1) as a mediator of find-me signal/nucleotide release from apoptotic cells. Pharmacological inhibition and siRNA-mediated knockdown of PANX1 led to decreased nucleotide release and monocyte recruitment by apoptotic cells. Conversely, PANX1 overexpression enhanced nucleotide release from apoptotic cells and phagocyte recruitment. Patch-clamp recordings showed that PANX1 was basally inactive, and that induction of PANX1 currents occurred only during apoptosis. Mechanistically, PANX1 itself was a target of effector caspases (caspases 3 and 7), and a specific caspase-cleavage site within PANX1 was essential for PANX1 function during apoptosis. Expression of truncated PANX1 (at the putative caspase cleavage site) resulted in a constitutively open channel. PANX1 was also important for the 'selective' plasma membrane permeability of early apoptotic cells to specific dyes. Collectively, these data identify PANX1 as a plasma membrane channel mediating the regulated release of find-me signals and selective plasma membrane permeability during apoptosis, and a new mechanism of PANX1 activation by caspases.
- Subjects
ELECTRIC properties of cell membranes; APOPTOSIS; PHAGOCYTES; ULTRAFILTRATION; NUCLEOTIDES; GENETICS
- Publication
Nature, 2010, Vol 467, Issue 7317, p863
- ISSN
0028-0836
- Publication type
Article
- DOI
10.1038/nature09413