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Endothelial gap junction proteins show type‐specific differences in oligomerization
Author(s) -
Koval Michael,
Smith Tekla,
Mohankumar Aditi,
Minogue Peter J,
Berthoud Viviana M,
Beyer Eric C
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a911-c
Subject(s) - endoplasmic reticulum , gap junction , connexin , asparagine , homomeric , chemistry , er retention , lysine , microbiology and biotechnology , hela , transmembrane protein , biochemistry , biophysics , cell , biology , amino acid , receptor , protein subunit , gene , intracellular , mutant
Cx37, Cx40 and Cx43 are gap junction proteins (connexins) expressed by vascular endothelial cells. Although these connexins can hetero‐oligomerize with each other, Cx37 is targeted to specific classes of endothelial cell‐cell junctions. Differences in oligomerization have the potential to help control connexin targeting. Using a di‐lysine based endoplasmic reticulum (ER) retention motif (HKKSL), we found that an arginine at position 153 (R153) near the third transmembrane domain is critical to stabilize monomeric Cx43 in the ER. R153 is of particular interest, since it is not present in either Cx37 or Cx40; the comparable residue is glycine (G) in Cx37 and asparagine (N) in Cx40. Similar to Cx43‐HKKSL a “Cx40‐like” construct (Cx43R153N‐HKKSL) was retained in the ER as monomers when expressed by HeLa cells. In contrast, a “Cx37‐like” construct (Cx43R153G‐HKKSL) showed a sucrose gradient fractionation profile with complexes in a size range that suggest partial to complete oligomerization. Cx37‐HKKSL had a gradient profile similar to Cx43R153G‐HKKSL. Thus, Cx37 is not as tightly stabilized as monomers in the ER as compared to Cx40 or Cx43. This suggests a model in which prior oligomerization of Cx37 in an early compartment of the secretory pathway may promote the formation of Cx37 homomeric channels in endothelial cells. These, in turn, could then be differentially sorted from channels containing Cx40 and/or Cx43.