The mechanism of connexin assembly into connexons has been well characterized. Two different types of connexons can be formed. A connexon containing six identical connexin molecules is referred to as an homomeric connexon, while a connexon containing at least two different connexin molecules is referred to as an heteromeric connexon. The connexin molecules making up an heteromeric connexon appear to belong to only one subgroup (alpha or beta); heteromeric connexons containing both alpha and beta subunits have not yet been observed. Indeed, an intrinsic signal in four amino acid positions appears to confer different physicochemical characteristics to certain connexins in the alpha and beta groups (Lagr et al., 2003). These intrinsic signals are Cx specific, however (see Gemel et al., 2006). Therefore, additional yet unknown signals are required to regulate connexin compatibility and hetero-oligomerization.
The identification of the subcellular location at which gap junction assembly occurs has proven difficult. One explanation for this difficulty may be that the location of oligomerization for each connexon varies depending upon Cx type or cell type. Oligomerization has been observed after ER membrane insertion (Cx43, Cx32, Cx26) (Falk et al., 1997; Ahmad et al., 1999; Ahmad and Evans, 2002), in the ER-Golgi-intermediate compartment (ERGIC) (Cx32) (Diez et al. 1999) and inside the trans-Goligi network (Cx43) (Musil and Goodenough, 1993).