TY - JOUR
T1 - ERp29 restricts connexin43 oligomerization in the endoplasmic reticulum
AU - Das, Shamie
AU - Smith, Tekla D.
AU - Das Sarma, Jayasri
AU - Ritzenthaler, Jeffrey D.
AU - Maza, Jose
AU - Kaplan, Benjamin E.
AU - Cunningham, Leslie A.
AU - Suaud, Laurence
AU - Hubbard, Michael J.
AU - Rubenstein, Ronald C.
AU - Koval, Michael
PY - 2009/5/15
Y1 - 2009/5/15
N2 - Connexin43 (Cx43) is a gap junction protein that forms multimeric channels that enable intercellular communication through the direct transfer of signals and metabolites. Although most multimeric protein complexes form in the endoplasmic reticulum (ER), Cx43 seems to exit from the ER as monomers and subsequently oligomerizes in the Golgi complex. This suggests that one or more protein chaperones inhibit premature Cx43 oligomerization in the ER. Here, we provide evidence that an ER-localized, 29-kDa thioredoxin-family protein (ERp29) regulates Cx43 trafficking and function. Interfering with ERp29 function destabilized monomeric Cx43 oligomerization in the ER, caused increased Cx43 accumulation in the Golgi apparatus, reduced transport of Cx43 to the plasma membrane, and inhibited gap junctional communication. ERp29 also formed a specific complex with monomeric Cx43. Together, this supports a new role for ERp29 as a chaperone that helps stabilize monomeric Cx43 to enable oligomerization to occur in the Golgi apparatus.
AB - Connexin43 (Cx43) is a gap junction protein that forms multimeric channels that enable intercellular communication through the direct transfer of signals and metabolites. Although most multimeric protein complexes form in the endoplasmic reticulum (ER), Cx43 seems to exit from the ER as monomers and subsequently oligomerizes in the Golgi complex. This suggests that one or more protein chaperones inhibit premature Cx43 oligomerization in the ER. Here, we provide evidence that an ER-localized, 29-kDa thioredoxin-family protein (ERp29) regulates Cx43 trafficking and function. Interfering with ERp29 function destabilized monomeric Cx43 oligomerization in the ER, caused increased Cx43 accumulation in the Golgi apparatus, reduced transport of Cx43 to the plasma membrane, and inhibited gap junctional communication. ERp29 also formed a specific complex with monomeric Cx43. Together, this supports a new role for ERp29 as a chaperone that helps stabilize monomeric Cx43 to enable oligomerization to occur in the Golgi apparatus.
UR - http://www.scopus.com/inward/record.url?scp=66249145769&partnerID=8YFLogxK
U2 - 10.1091/mbc.E08-07-0790
DO - 10.1091/mbc.E08-07-0790
M3 - Article
C2 - 19321666
AN - SCOPUS:66249145769
SN - 1059-1524
VL - 20
SP - 2593
EP - 2604
JO - Molecular biology of the cell
JF - Molecular biology of the cell
IS - 10
ER -