Gap junction and hemichannel‐independent actions of connexins on cell and tissue functions – An update

Abstract

Connexins, a family of transmembrane proteins, are components of both gap junction channels and hemichannels, which mediate the exchange of ions and small molecules between adjacent cells, and between the inside and outside of the cell, respectively. Substantial advancements have been made in the comprehension of the role of gap junctions and hemichannels in coordinating cellular events. In recent years, a plethora of studies demonstrate a role of connexin proteins in the regulation of tissue homeostasis that occurs independently of their channel activities. This is shown in the context of cell growth, adhesion, migration, apoptosis, and signaling. The major mechanisms of these channel-independent activities still remain to be discovered. In this review, we provide an updated overview on the current knowledge of gap junction- and hemichannel-independent functions of connexins, in particular, their effects on tumorigenesis, neurogenesis and disease development.

Connexin 30 controls the extension of astrocytic processes into the synaptic cleft through an unconventional non-channel function

“…In agreement with this possibility, the GLT current evoked in Cx30 -/-astrocytes by and tumorigenicity by interacting with a plethora of connexin-associated proteins including cytoskeletal elements, enzymes (kinases and phosphatases), adhesion molecules, and signaling molecules [7] . Consequently, Interestingly, Cx30 has been shown to interact with cytoskeletal proteins that regulate cell adhesion and motility [8] .…”

“…Histological studies indicated important morphological changes in astrocytes from Cx30 -/-mice. Although the role of the C-terminal tail of connexins in the regulation of cell morphology has been described, mainly in the context of cell adhesion, migration, and proliferation during disease and cancer development [7] , this study is the fi rst to demonstrate its role in a physiological process.…”

“…However, how the C-terminus of connexins control cell behavior remains elusive [7] . It would be interesting to determine the precise molecular mechanisms by which the C-terminal tail of Cx30 controls the development of membrane protrusions in astrocytic processes.…”

Dysfunction in gap junction intercellular communication induces aberrant behavior of the inner cell mass and frequent collapses of expanded blastocysts in mouse embryos

“…Gap junctions (GJs) are involved in direct signal transduction between adhering adjacent blastomeres. Gap junction intercellular communication (GJIC) transmits various signals including activation of the Hippo signaling pathway, which is associated with differentiation of the trophectoderm (TE) / inner cell mass (ICM) [3]. GJs have also been suggested to play a role in blastocoel formation of the preimplantation embryo [4].…”

Proteomic Analysis of Connexin 43 Reveals Novel Interactors Related to Osteoarthritis

“…Initially, the cellular functions of Cxs were attributed exclusively to direct cell-to-cell diffusion; however, some Cx functions seem to be independent of channel function (18). In fact, several reports have suggested that the Cx43 complex might fulfil functions that are not necessarily related to the control of GJIC.…”