Effects on Channel Properties and Induction of Cell Death Induced by C-terminal Truncations of Pannexin1 Depend on Domain Length

Effects on Channel Properties and Induction of Cell Death Induced by C-terminal Truncations of... Pannexin1 (Panx1) is an integral membrane protein and known to form multifunctional hexameric channels. Recently, Panx1 was identified to be responsible for the release of ATP and UTP from apoptotic cells after site-specific proteolysis by caspases 3/7. Cleavage at the carboxy-terminal (CT) position aa 376–379 irreversibly opens human Panx1 channels and leads to the release of the respective nucleotides resulting in recruitment of macrophages and in subsequent activation of the immunologic response. The fact that cleavage of the CT at this particular residues terminates in a permanently open channel raised the issue of functional relevance of the CT of Panx1 for regulating channel properties. To analyze the impact of the CT on channel gating, we generated 14 truncated versions of rat Panx1 cleaved at different positions in the C-terminus. This allowed elaboration of the influence of defined residues on channel formation, voltage-dependent gating, execution of cell mortality, and susceptibility to the Panx1 inhibitor carbenoxolone. We demonstrate that expression of Panx1 proteins, which were truncated to lengths between 370 and 393 residues, induces differential effects after expression in Xenopus laevis oocytes as well as in Neuro2A cells with strongest impact downstream the caspase 3/7 cleavage site. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

Effects on Channel Properties and Induction of Cell Death Induced by C-terminal Truncations of Pannexin1 Depend on Domain Length

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Publisher
Springer Journals
Copyright
Copyright © 2015 by Springer Science+Business Media New York
Subject
Life Sciences; Biochemistry, general; Human Physiology
ISSN
0022-2631
eISSN
1432-1424
D.O.I.
10.1007/s00232-014-9767-4
Publisher site
See Article on Publisher Site

Abstract

Pannexin1 (Panx1) is an integral membrane protein and known to form multifunctional hexameric channels. Recently, Panx1 was identified to be responsible for the release of ATP and UTP from apoptotic cells after site-specific proteolysis by caspases 3/7. Cleavage at the carboxy-terminal (CT) position aa 376–379 irreversibly opens human Panx1 channels and leads to the release of the respective nucleotides resulting in recruitment of macrophages and in subsequent activation of the immunologic response. The fact that cleavage of the CT at this particular residues terminates in a permanently open channel raised the issue of functional relevance of the CT of Panx1 for regulating channel properties. To analyze the impact of the CT on channel gating, we generated 14 truncated versions of rat Panx1 cleaved at different positions in the C-terminus. This allowed elaboration of the influence of defined residues on channel formation, voltage-dependent gating, execution of cell mortality, and susceptibility to the Panx1 inhibitor carbenoxolone. We demonstrate that expression of Panx1 proteins, which were truncated to lengths between 370 and 393 residues, induces differential effects after expression in Xenopus laevis oocytes as well as in Neuro2A cells with strongest impact downstream the caspase 3/7 cleavage site.

Journal

The Journal of Membrane BiologySpringer Journals

Published: Jan 8, 2015

References

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