Oligomerization of connexins into connexons

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. <br>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).

connexin组装成connexons的机制已得到充分阐明。可以形成两种不同类型的connexons。含有六个相同connexin分子的connexon被称为同源connexon，而含有至少两种不同connexin分子的connexon则被称为异源connexon。构成异源connexon的connexin分子似乎仅属于一个亚组（α或β）；同时含有α和β亚单位的异源connexons尚未观察到。实际上，在四个氨基酸位置上的固有信号似乎赋予α和β组中某些connexin不同的物理化学特性（Lagr等，2003年）。然而，这些固有信号是Cx特异性的（参见Gemel等，2006年）。因此，还需要额外的、尚未知的信号来调节connexin的兼容性和异源寡聚化。在确定gap junction组装发生的亚细胞位置方面遇到了困难。造成这一困难的一个可能解释是，每个connexon的寡聚化位置根据Cx类型或细胞类型而有所不同。在ER膜插入后（Cx43、Cx32、Cx26）（Falk等，1997年；Ahmad等，1999年；Ahmad和Evans，2002年）观察到寡聚化，在ER-Golgi中间区域（ERGIC）（Cx32）（Diez等，1999年）以及在内质网-高尔基体-转高尔基网络（Cx43）（Musil和Goodenough，1993年）内。