Structure, Regulation and Function of Gap Junctions in Liver

Abstract

Gap junctions are a specialized group of cell-to-cell junctions that mediate direct intercellular communication between cells. They arise from the interaction of 2 hemichannels of adjacent cells, which in turn are composed of 6 connexin proteins. In liver, gap junctions are predominantly found in hepatocytes and play critical roles in virtually all phases of the hepatic life cycle, including cell growth, differentiation, liver-specific functionality and cell death. Liver gap junctions are directed through a broad variety of mechanisms ranging from epigenetic control of connexin expression to posttranslational regulation of gap junction activity. This paper reviews established and novel aspects regarding the architecture, control and functional relevance of liver gap junctions.

Tramadol attenuates the sensitivity of glioblastoma to temozolomide through the suppression of Cx43‑mediated gap junction intercellular communication

“…Gap junctions, formed by Cxs, have important roles in maintenance of tissue homeostasis and regulation of cell growth and differentiation (3,37). Reduced expression and disruption of gap junction function is usually correlated with tumorigenic phenotypes in various cancer cells.…”

“…LINGZHI WANG 1* , YUExIA PENG 2* , JIANxIN PENG 3 , MIN SHAO 2 , LI MA 4 , ZHUOLI ZHU 1 , GUOCHENG ZHONG 1 , ZHENGYUAN xIA 1 and HUANSEN HUANG 1 and are named by their molecular weights. Among them, Cx43 is the most ubiquitously expressed and is critical for regulating biological and pathological processes in a variety of tissues (2,3).…”

Platelet-Rich Plasma Modulates Gap Junction Functionality and Connexin 43 and 26 Expression During TGF-β1–Induced Fibroblast to Myofibroblast Transition: Clues for Counteracting Fibrosis

“…The gap junction (GJ) channels are dynamic membrane domains built of two docking hemichannels called connexons assembled in the plasma membranes of two adjacent cells. Each connexon is a hexameric structure consisting of six transmembrane proteins named connexins (Cxs) that may have different molecular weights [49] and form an aqueous pore. The opening of these channels allows the flow of ions and small molecules (less than 1000 MW molecular weight size fractions) such as sugars, amino acids, oxygen, as well as second messengers such as cAMP, inositol phosphates, and calcium directly from one cell to another.…”

Cholestasis Differentially Affects Liver Connexins

“…Gap junctions arise from the interaction of two hemichannels of neighboring cells, which in turn are built up by six connexin (Cx) proteins. More than 20 different connexin proteins have been identified in humans and rodents, and all are expressed in a cell type-specific way [9,10]. In the liver, hepatocytes mainly produce Cx32 and small quantities of Cx26, while non-parenchymal liver cells typically harbor Cx43 [11][12][13].…”