The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Pannexin 1, an ATP Release Channel, Is Activated by Caspase Cleavage of Its Pore-associated C-terminal Autoinhibitory Region
Open accessAbstract
Pannexin 1 (PANX1) channels mediate release of ATP, a "find-me" signal that recruits macrophages to apoptotic cells; PANX1 activation during apoptosis requires caspase-mediated cleavage of PANX1 at its C terminus, but how the C terminus inhibits basal channel activity is not understood. Here, we provide evidence suggesting that the C terminus interacts with the human PANX1 (hPANX1) pore and that cleavage-mediated channel activation requires disruption of this inhibitory interaction. Basally silent hPANX1 channels localized on the cell membrane could be activated directly by protease-mediated C-terminal cleavage, without additional apoptotic effectors. By serial deletion, we identified a C-terminal region just distal to the caspase cleavage site that is required for inhibition of hPANX1; point mutations within this small region resulted in partial activation of full-length hPANX1. Consistent with the C-terminal tail functioning as a pore blocker, we found that truncated and constitutively active hPANX1 channels could be inhibited, in trans, by the isolated hPANX1 C terminus either in cells or when applied directly as a purified peptide in inside-out patch recordings. Furthermore, using a cysteine cross-linking approach, we showed that relief of inhibition following cleavage requires dissociation of the C terminus from the channel pore. Collectively, these data suggest a mechanism of hPANX1 channel regulation whereby the intact, pore-associated C terminus inhibits the full-length hPANX1 channel and a remarkably well placed caspase cleavage site allows effective removal of key inhibitory C-terminal determinants to activate hPANX1.
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Cites
Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance
Elliott, M. R., Chekeni, F. B., Trampont, P. C., Lazarowski, E. R., Kadl, A., Walk, S. F., Park, D., Woodson, R. I., Ostankovich, M., Sharma, P., et al. (2009) · Nature · doi:10.1038/nature08296 · Cited by 1,654
Self-citationBiophysical and Molecular Mechanisms of Shaker Potassium Channel Inactivation
Hoshi, T., Zagotta, W. N., & Aldrich, R. W. (1990) · Science · doi:10.1126/science.2122519 · Cited by 1,538
Pannexin 1 channels mediate ‘find-me’ signal release and membrane permeability during apoptosis
Chekeni, F. B., Elliott, M. R., Sandilos, J. K., Walk, S. F., Kinchen, J. M., Lazarowski, E. R., Armstrong, A. J., Penuela, S., Laird, D. W., Salvesen, G. S., et al. (2010) · Nature · doi:10.1038/nature09413 · Cited by 1,120
Self-citationPannexin membrane channels are mechanosensitive conduits for ATP
Bao, L., Locovei, S., & Dahl, G. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.07.009 · Cited by 802
Restoration of Inactivation in Mutants of Shaker Potassium Channels by a Peptide Derived from ShB
Zagotta, W. N., Hoshi, T., & Aldrich, R. W. (1990) · Science · doi:10.1126/science.2122520 · Cited by 758
Structure of the connexin 26 gap junction channel at 3.5 Å resolution
Maeda, S., Nakagawa, S., Suga, M., Yamashita, E., Oshima, A., Fujiyoshi, Y., & Tsukihara, T. (2009) · Nature · doi:10.1038/nature07869 · Cited by 725
Destruction of Sodium Conductance Inactivation in Squid Axons Perfused with Pronase
Armstrong, C. M., Bezanilla, F., & Rojas, E. (1973) · The Journal of General Physiology · doi:10.1085/jgp.62.4.375 · Cited by 538
The Pannexin 1 Channel Activates the Inflammasome in Neurons and Astrocytes
Silverman, W. R., de Rivero Vaccari, J. P., Locovei, S., Qiu, F., Carlsson, S. K., Scemes, E., Keane, R. W., & Dahl, G. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.004804 · Cited by 533
Pannexin-1 Is Required for ATP Release during Apoptosis but Not for Inflammasome Activation
Qu, Y., Misaghi, S., Newton, K., Gilmour, L. L., Louie, S., Cupp, J. E., Dubyak, G. R., Hackos, D., & Dixit, V. M. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100478 · Cited by 363
Pannexin channels are not gap junction hemichannels
Sosinsky, G. E., Boassa, D., Dermietzel, R., Duffy, H. S., Laird, D. W., MacVicar, B., Naus, C. C., Penuela, S., Scemes, E., Spray, D. C., et al. (2011) · Channels · doi:10.4161/chan.5.3.15765 · Cited by 349
Cited by
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Cekic, C., & Linden, J. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.4 · Cited by 787
Molecular mechanisms of ATP secretion during immunogenic cell death
Martins, I., Wang, Y., Michaud, M., Ma, Y., Sukkurwala, A. Q., Shen, S., Kepp, O., Métivier, D., Galluzzi, L., Perfettini, J.-L., et al. (2014) · Cell Death & Differentiation · doi:10.1038/cdd.2013.75 · Cited by 563
Metabolic regulatory crosstalk between tumor microenvironment and tumor-associated macrophages
Chen, D., Zhang, X., Li, Z., & Zhu, B. (2021) · Theranostics · doi:10.7150/thno.51777 · Cited by 390
Living on the Edge: Efferocytosis at the Interface of Homeostasis and Pathology
Morioka, S., Maueröder, C., & Ravichandran, K. S. (2019) · Immunity · doi:10.1016/j.immuni.2019.04.018 · Cited by 391
Self-citationMechanisms of ATP Release by Inflammatory Cells
Dosch, M., Gerber, J., Jebbawi, F., & Beldi, G. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19041222 · Cited by 283
Metadata
- Authors
- Sandilos, J. K., Chiu, Y.-H., Chekeni, F. B., Armstrong, A. J., Walk, S. F., Ravichandran, K. S., & Bayliss, D. A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 287
- Issue
- 14
- Pages
- 11303-11311
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2029913563
- Cited by
- 302
- References
- 29
- FWCI
- 13.28
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: Pannexin 1, an ATP Release Channel, Is Activated by Caspase Cleavage of Its Pore-associated C-terminal Autoinhibitory Region. https://app.cochat.ai/papers/10.1074/jbc.m111.323378
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- Sandilos, J. K., Chiu, Y.-H., Chekeni, F. B., Armstrong, A. J., Walk, S. F., Ravichandran, K. S., & Bayliss, D. A. (2012). Pannexin 1, an ATP Release Channel, Is Activated by Caspase Cleavage of Its Pore-associated C-terminal Autoinhibitory Region. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m111.323378
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