Pannexins, distant relatives of the connexin family with specific cellular functions?

Abstract

Intercellular communication (IC) is mediated by gap junctions (GJs) and hemichannels, which consist of proteins. This has been particularly well documented for the connexin (Cx) family. Initially, Cxs were thought to be the only proteins capable of GJ formation in vertebrates. About 10 years ago, however, a new GJ-forming protein family related to invertebrate innexins (Inxs) was discovered in vertebrates, and named the pannexin (Panx) family. Panxs, which are structurally similar to Cxs, but evolutionarily distinct, have been shown to be co-expressed with Cxs in vertebrates. Both protein families show distinct properties and have their own particular function. Identification of the mechanisms that control Panx channel gating is a major challenge for future work. In this review, we focus on the specific properties and role of Panxs in normal and pathological conditions.

Pannexin 1, an ATP Release Channel, Is Activated by Caspase Cleavage of Its Pore-associated C-terminal Autoinhibitory Region

“…Because hPANX1 appears to be critical for find-me signal release and prompt clearance of apoptotic cells (5), such compounds could find use in conditions where manipulation of cell clearance may be advantageous (e.g. autoimmune disease and cancer) (2,29,30).…”

“…Statistical analysis was by 2 analysis, Student's t test, or analysis of variance, with post hoc comparisons made using a Bonferroni-corrected t test; differences between groups were considered significant if p Ͻ 0.05.…”

“…Pannexins are a relatively recently identified family of channels, distantly related by sequence to the gap junction-forming mammalian connexins and invertebrate innexins, with similar putative transmembrane topology (1,2). Initial expectations that pannexins might also incorporate into intercellular gap junctions have given way to current views that they instead form membrane channels (3).…”

“…Initial expectations that pannexins might also incorporate into intercellular gap junctions have given way to current views that they instead form membrane channels (3). Among the three members of the pannexin family, pannexin 1 (PANX1) 2 has garnered the most attention. PANX1 forms a plasma membrane ion channel with a large single channel conductance (ϳ500 picosiemens) and a pore that permits permeation by small molecules up to 1 kDa in size (2,4).…”

“…Among the three members of the pannexin family, pannexin 1 (PANX1) 2 has garnered the most attention. PANX1 forms a plasma membrane ion channel with a large single channel conductance (ϳ500 picosiemens) and a pore that permits permeation by small molecules up to 1 kDa in size (2,4). PANX1 channels allow efflux of signaling nucleotides, ATP and UTP, and influx of specific dyes that are used to visualize cells undergoing apoptosis (e.g.…”