SCAM analysis of Panx1 suggests a peculiar pore structure

Junjie Wang, Gerhard Dahl

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Vertebrates express two families of gap junction proteins: the well-characterized connexins and the pannexins. In contrast to connexins, pannexins do not appear to form gap junction channels but instead function as unpaired membrane channels. Pannexins have no sequence homology to connexins but are distantly related to the invertebrate gap junction proteins, innexins. Despite the sequence diversity, pannexins and connexins form channels with similar permeability properties and exhibit similar membrane topology, with two extracellular loops, four transmembrane (TM) segments, and cytoplasmic localization of amino and carboxy termini. To test whether the similarities extend to the pore structure of the channels, pannexin 1 (Panx1) was subjected to analysis with the substituted cysteine accessibility method (SCAM). The thiol reagents maleimidobutyryl-biocytin and 2-trimethyl- ammonioethyl- methanethiosulfonate reacted with several cysteines positioned in the external portion of the first TM segment (TM1) and the first extracellular loop. These data suggest that portions of TM1 and the first extracellular loop line the outer part of the pore of Panx1 channels. In this aspect, the pore structures of Panx1 and con-nexin channels are similar. However, although the inner part of the pore is lined by amino-terminal amino acids in connexin channels, thiol modification was detected in carboxyterminal amino acids in Panx1 channels by SCAM analysis. Thus, it appears that the inner portion of the pores of Panx1 and connexin channels may be distinct.

Original languageEnglish
Pages (from-to)515-527
Number of pages13
JournalJournal of General Physiology
Volume136
Issue number5
DOIs
StatePublished - Nov 1 2010

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Connexins
Cysteine
Amino Acids
Sulfhydryl Reagents
Gap Junctions
Invertebrates
Sequence Homology
Ion Channels
Sulfhydryl Compounds
Vertebrates
Permeability
Membranes

ASJC Scopus subject areas

  • Physiology

Cite this

SCAM analysis of Panx1 suggests a peculiar pore structure. / Wang, Junjie; Dahl, Gerhard.

In: Journal of General Physiology, Vol. 136, No. 5, 01.11.2010, p. 515-527.

Research output: Contribution to journalArticle

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