Pannexin 1 channels mediate 'find-me' signal release and membrane permeability during apoptosis.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Chekeni, FB; Elliott, MR; Sandilos, JK; Walk, SF; Kinchen, JM; Lazarowski, ER; Armstrong, AJ; Penuela, S; Laird, DW; Salvesen, GS; Isakson, BE; Bayliss, DA; Ravichandran, KS

Published Date

  • October 14, 2010

Published In

Volume / Issue

  • 467 / 7317

Start / End Page

  • 863 - 867

PubMed ID

  • 20944749

Pubmed Central ID

  • 20944749

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

Digital Object Identifier (DOI)

  • 10.1038/nature09413

Language

  • eng

Conference Location

  • England