Connections with connexins: the molecular basis of direct intercellular signaling

Abstract

Adjacent cells share ions, second messengers and small metabolites through intercellular channels which are present in gap junctions. This type of intercellular communication permits coordinated cellular activity, a critical feature for organ homeostasis during development and adult life of multicellular organisms. Intercellular channels are structurally more complex than other ion channels, because a complete cell-to-cell channel spans two plasma membranes and results from the association of two half channels, or connexons, contributed separately by each of the two participating cells, Each connexon, in turn, is a multimeric assembly of protein subunits. The structural proteins comprising these channels, collectively called connexins, are members of a highly related multigene family consisting of at least 13 members.

Connexins, cell motility, and the cytoskeleton

“…Combination of different Cx subtypes can lead to the formation of homomeric and heteromeric connexons [Bruzzone et al, 1996]. Different criteria conveyed by the primary structure of the Cxs and/or associated proteins are considered to be responsible for homo-or heter- ooligomerization [Koval, 2006].…”

Loss-of-function GJA12/Connexin47 mutations cause Pelizaeus–Merzbacher-like disease

“…Gap junction communication (GJC) facilitates the diffusion of ions and small molecules (less than 1000 Da) between two apposed cells, thereby enabling electrical coupling, metabolic cooperation, and spatial buffering of ions (Bruzzone et al 1996). The molecular basis of GJC is the gap junction plaque, an aggregation of tens to thousands of individual channels.…”

Early embryonic expression of ion channels and pumps in chick and Xenopus development

“…Because gap junctions are subject to numerous regulatory steps at the posttranslational level, functional electrophysiology studies are needed to determine what open junctional paths exist for various types of ions during different stages of embryogenesis. That gap-junction gating and selectivity properties depend greatly on which connexin family members comprise the junction (Elfgang et al, 1995;Bruzzone et al, 1996b;Meda, 2000) further underscores the necessity for a comprehensive understanding of which connexins are expressed in which embryonic cells during patterning. Overlapping patterns of connexin expression are consistent with the presence of heteromeric or heterotypic gap junctions, which could possess complex gating properties not present in either connexin alone.…”