In:
Molecular Biology of the Cell, American Society for Cell Biology (ASCB), Vol. 16, No. 7 ( 2005-07), p. 3260-3272
Abstract:
P2X 7 is a bifunctional receptor (P2X 7 R) for extracellular ATP that, depending on the level of activation, forms a cation-selective channel or a large conductance nonselective pore. The P2X 7 R has a strong proapoptotic activity but can also support growth. Here, we describe the mechanism involved in growth stimulation. Transfection of P2X 7 R increases resting mitochondrial potential (Δψ mt ), basal mitochondrial Ca 2+ ([Ca 2+ ] mt ), intracellular ATP content, and confers ability to grow in the absence of serum. These changes require a full pore-forming function, because they are abolished in cells transfected with a mutated P2X 7 R that retains channel activity but cannot form the nonselective pore, and depend on an autocrine/paracrine tonic stimulation by secreted ATP. On the other hand, sustained stimulation of P2X 7 R causes a Δψ mt drop, a large increase in [Ca 2+ ] mt , mitochondrial fragmentation, and cell death. These findings reveal a hitherto undescribed mechanism for growth stimulation by a plasma membrane pore.
Type of Medium:
Online Resource
ISSN:
1059-1524
,
1939-4586
DOI:
10.1091/mbc.e04-11-1025
Language:
English
Publisher:
American Society for Cell Biology (ASCB)
Publication Date:
2005
detail.hit.zdb_id:
1474922-1
SSG:
12
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