Membrane insertion of gap junction connexins: polytopic channel forming membrane proteins

Analysis of the conditions that were associated with the proteolytic processing indicates that the connexins were not processed by one of the known proteolytic activities that function in the degradation of misfolded or improperly oligomerized proteins in the ER, a process generally referred to as "rapid ER degradation" (Amara et al., 1989; Klausner and Sitia, 1990; Bonifacino and Lippincott-Schwartz, 1991) . First, these proteases normally do not process proteins in such a rapid reaction that is directly linked to membrane integration, such as observed in this study for the connexins (Fig. 1) . Second, the proteolytic cleavage of the connexins could not be prevented by cysteine and serine protease inhibitors such as TPCK, TLCK, leupeptin, or E64 (Fig. 6 B) , and these inhibitors have been reported to block the known enzymes related to this process (Wikstr/Sm and Lodish, 1991; Urade and Kito, 1992; Yuk and Lodish, 1993) .