The membrane protein Pannexin1 forms two open-channel conformations depending on the mode of activation

Junjie Wang, Cinzia Ambrosi, Feng Qiu, David G. Jackson, Gina Sosinsky, Gerhard Dahl

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Pannexin1 (Panx1) participates in several signaling events that involve adenosine triphosphate (ATP) release, including the innate immune response, ciliary beat in airway epithelia, and oxygen supply in the vasculature. The view that Panx1 formsa large ATP release channel has been challenged by the association of a low-conductance, small anion-selective channel with the presence of Panx1. We showed that Panx1 membrane channels can function in two distinct modes with different conductances and permeabilities when heterologously expressed in Xenopus oocytes. When stimulated by potassium ions (K+), Panx1 formed a high-conductance channel of ∼500 pS that was permeable to ATP. Various physiological stimuli can induce this ATP-permeable conformation of the channel in several cell types. In contrast, the channel had a low conductance (∼50 pS) with no detectable ATP permeability when activated by voltage in the absence of K+. The two channel states were associated with different reactivities of the terminal cysteine of Panx1 to thiol reagents, suggesting different conformations. Single-particle electron microscopic analysis revealed that K+ stimulated the formation of channels with a larger pore diameter than those formed in the absence of K+. These data suggest that different stimuli lead to distinct channel structures with distinct biophysical properties.

Original languageEnglish (US)
Article numberra69
JournalScience Signaling
Volume7
Issue number335
DOIs
StatePublished - Jul 22 2014

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'The membrane protein Pannexin1 forms two open-channel conformations depending on the mode of activation'. Together they form a unique fingerprint.

  • Cite this