title: ERp29 restricts Connexin43 oligomerization in the endoplasmic reticulum.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Shamie
authors.initials: S
authors.lastname: Das
authors.forename: Tekla D
authors.initials: TD
authors.lastname: Smith
authors.forename: Jayasri Das
authors.initials: JD
authors.lastname: Sarma
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Ritzenthaler
authors.forename: Jose
authors.initials: J
authors.lastname: Maza
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Kaplan
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Cunningham
authors.forename: Laurence
authors.initials: L
authors.lastname: Suaud
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hubbard
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Rubenstein
authors.forename: Michael
authors.initials: M
authors.lastname: Koval