The role of the Cx43 C-terminus in GJ plaque formation and internalization
- 作者：Praween Wayakanona ; b ; Rajib Bhattacharjeea ; b ; Ken-ichi Nakahamaa ; nakacell@tmd.ac.jp ; Ikuo Moritaa ; b
- 关键词：Gap junction (GJ) ; Connexin 43 (Cx43) ; Annular gap junction (AGJ) ; C-terminus
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2012
- 期刊代码：159_0006291x
- 类别：bio
- 出版时间：6 April, 2012
- 卷：420
- 期：2
- 页码：456-461
- 文件大小：1160 K
摘要
Connexin 43 (Cx43) is a major gap junction (GJ) protein found in many mammalian cell types. The C-terminal (CT) domain of Cx43 has unique characteristics in terms of amino acid (aa) sequence and its length differs from other connexins. This CT domain can be associated with protein partners to regulate GJ assembly and degradation, which results in the direct control of gap junction intercellular communication (GJIC). However, the essential roles of the CT regions involved in these mechanisms have not been fully elucidated. In this study, we aimed to investigate the specific regions of Cx43CT involved in GJ formation and internalization. Wild type Cx43(382aa) and 10 CT truncated mutants were stably expressed in HeLa cells as GFP or DsRed tagged proteins. First, we found that the deletion of 235-382aa from Cx43 resulted in failure to make GJ and establish GJIC. Second, the Cx43 with 242-382aa CT deletion could form functional GJs and be internalized as annular gap junctions (AGJs). However, the plaques consisting of Cx43 with CT deletions (螖242-382aa to 螖271-382aa) were longer than the plaques consisting of Cx43 with CT deletions (螖302-382aa). Third, co-culture experiments of cells expressing wild type Cx43(382) with cells expressing Cx43CT mutants revealed that the directions of GJ internalization were dependent on the length of the respective CT. Moreover, a specific region, 325-342aa residues of Cx43, played an important role in the direction of GJ internalization. These results showed the important roles of the Cx43 C-terminus in GJ expression and its turnover.