Hanne Verswyvel

Chapter 5 │ Page 164 2. GJs STRUCTURE AND COMPOSITION The first time that GJs were isolated and characterized by X-ray di raction analysis was in 1972 [46], and since then, it is known that three families of GJs proteins make up this structure: innexins, pannexins, and connexins [47,48]. Of these three, the connexin (Cx) family, first described in 1974 [49], is the most abundant in vertebrate animals [50]. The human Cx protein family contains 21 members, named according to their relative molecular mass [51,52]. Each Cx is a transmembrane (TM) protein with four TM domains in the α-helical conformation (TM1 to TM4) (Figure 2a). These domains are connected by two extracellular loops (EL-1 and EL-2) and one cytoplasmic loop (CL), containing an amino (NT) and carboxyl terminus (CT) in the cytoplasm (Figure 2b) [53]. Whereas the size of the CT domain is the major determinant of Cx molecular mass, which can range from 23 to 62 kDa, the NT domain is of similar length in all Cxs (first 22-23 amino acids), with their first part present in an α-helical conformation. Although present on almost all human cells [54,55], Cx isotype expression is usually restricted to a certain organ, tissue, or cell type. However, certain Cx proteins, such as Cx43, are more ubiquitously expressed. Figure 2: Schematic representation of a Cx43 protein in a lipid bilayer membrane. (A) The transmembrane domains TM1, TM2, TM3, and TM4 are represented in blue, red, orange and yellow colors, respectively. (B) The extracellular (EL-1 and EL-2) and cytoplasmic (CL) loops are represented in pink, black, and purple colors, respectively. The amino (NT) and carboxyl (CT) terminus are represented in green and gray colors, respectively. For the sake of clarity, only a small part of the CT domain is represented.

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