| Pannexin 1 channels mediate 'find-me' signal release and membrane permeability during apoptosis. | |
| | |
MedLine Citation:
|
PMID: 20944749 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
Faraaz B Chekeni; Michael R Elliott; Joanna K Sandilos; Scott F Walk; Jason M Kinchen; Eduardo R Lazarowski; Allison J Armstrong; Silvia Penuela; Dale W Laird; Guy S Salvesen; Brant E Isakson; Douglas A Bayliss; Kodi S Ravichandran |
Related Documents
:
|
15902419 - Toxicant-induced er-stress and caspase activation in the olfactory mucosa. 14985459 - Staurosporine induces apoptosis of melanoma by both caspase-dependent and -independent ... 20682709 - X-linked inhibitor of apoptosis: a chemoresistance factor or a hollow promise. 14990979 - Cddo induces apoptosis via the intrinsic pathway in lymphoid cells. 12966169 - Inhibition of caspase activation and a requirement for nf-kappab function in the toxopl... 18175929 - Induction of serum amyloid a genes is associated with growth and apoptosis of hc11 mamm... 9107409 - The molecular control of granulocytes and macrophages. 16313349 - Interplay between interferon and other cytokine systems in bone metabolism. 9731219 - Cholesterol oxides induce programmed cell death in microglial cells. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Nature Volume: 467 ISSN: 1476-4687 ISO Abbreviation: Nature Publication Date: 2010 Oct |
Date Detail:
|
Created Date: 2010-10-14 Completed Date: 2010-12-01 Revised Date: 2011-07-27 |
Medline Journal Info:
|
Nlm Unique ID: 0410462 Medline TA: Nature Country: England |
Other Details:
|
Languages: eng Pagination: 863-7 Citation Subset: IM |
Affiliation:
|
Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia 22908, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adenosine Triphosphate
/
metabolism,
secretion Apoptosis* / drug effects Carbenoxolone / pharmacology Caspase 3 / metabolism Caspase 7 / metabolism Cell Membrane Permeability / physiology* Chemotaxis / drug effects Connexins / antagonists & inhibitors, deficiency, genetics, metabolism* Electric Conductivity Humans Jurkat Cells Nerve Tissue Proteins / antagonists & inhibitors, deficiency, genetics, metabolism* Patch-Clamp Techniques Phagocytes / cytology, physiology Phagocytosis* / drug effects Uridine Triphosphate / metabolism, secretion |
| Grant Support | |
ID/Acronym/Agency:
|
F30 HL096400-03/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Connexins; 0/Nerve Tissue Proteins; 0/PANX1 protein, human; 56-65-5/Adenosine Triphosphate; 5697-56-3/Carbenoxolone; 63-39-8/Uridine Triphosphate; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 7 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Non-muscle myosin IIA is a functional entry receptor for herpes simplex virus-1.
Next Document: The proteasome antechamber maintains substrates in an unfolded state.