The KDEL receptor has a role in the biogenesis and trafficking of the epithelial sodium channel (ENaC).

Endoplasmic reticulum protein of 29 kDa (ERp29) is a thioredoxin-homologous endoplasmic reticulum (ER) protein that regulates the biogenesis of cystic fibrosis transmembrane conductance regulator (CFTR) and the epithelial sodium channel (ENaC). ERp29 may promote ENaC cleavage and increased open probability by directing ENaC to the Golgi via coat complex II (COP II) during biogenesis. We hypothesized that ERp29's C-terminal KEEL ER retention motif, a KDEL variant that is associated with less robust ER retention, strongly influences its regulation of ENaC biogenesis. As predicted by our previous work, depletion of Sec24D, the cargo recognition component of COP II that we previously demonstrated to interact with ENaC, decreases ENaC functional expression without altering ß-ENaC expression at the apical surface. We then tested the influence of KDEL ERp29, which should be more readily retrieved from the proximal Golgi by the KDEL receptor (KDEL-R), and a KEEL-deleted mutant (ΔKEEL ERp29), which should not interact with the KDEL-R. ENaC functional expression was decreased by ΔKEEL ERp29 overexpression, whereas KDEL ERp29 overexpression did not significantly alter ENaC functional expression. Again, ß-ENaC expression at the apical surface was unaltered by either of these manipulations. Finally, we tested whether the KDEL-R itself has a role in ENaC forward trafficking and found that KDEL-R depletion decreases ENaC functional expression, again without altering ß-ENaC expression at the apical surface. These results support the hypothesis that the KDEL-R plays a role in the biogenesis of ENaC and in its exit from the ER through its association with COP II. The cleavage of the extracellular loops of the epithelial sodium channel (ENaC) α and γ subunits increases the channel's open probability and function. During ENaC biogenesis, such cleavage is regulated by the novel 29-kDa chaperone of the ER, ERp29. Our data here are consistent with the hypothesis that ERp29 must interact with the KDEL receptor to exert its regulation of ENaC biogenesis. The classically described role of the KDEL receptor is to retrieve ER-retained species from the proximal Golgi and return them to the ER via coat complex I machinery. In contrast, our data suggest a novel and important role for the KDEL receptor in the biogenesis and forward trafficking of ENaC.

Phytotoxicity of soluble graphitic nanofibers to model plant species.

Carbon nanomaterials are considered promising for applications in energy storage, catalysis, and electronics. This has motivated study of their potential environmental toxicity. Recently, a novel nanomaterial consisting of graphene oxide wrapped around a carbon nanotube (CNT) core was synthesized. The resulting soluble graphitic nanofibers were found to have superior catalytic properties, which could result in their use in fuel cells. Before this material undergoes widespread use, its environmental toxicity must be determined because of its aqueous solubility. The authors used the plant species Lolium multiflorum, Solanum lycopersicum, and Lactuca sativa to study the toxicity of the soluble graphitic nanofibers, as well as multiwalled carbon nanotubes (MWCNTs) and graphene oxide, all synthesized in-house. Soluble graphitic nanofiber-exposed plant roots and shoots showed decreased growth, with roots showing more toxicity than shoots. Decreased pH of nanomaterial solutions corresponded to insignificantly decreased root growth, suggesting that another mechanism of toxicity must exist. Agglomeration and adsorption of soluble graphitic nanofibers onto the roots likely caused the remaining toxicity because a gray layer could be seen around the surface of the root. Multiwalled carbon nanotubes showed little toxicity over the concentration range tested, whereas graphene oxide showed a unique pattern of high toxicity at both the lowest and highest concentrations tested. Overall, soluble graphitic nanofibers showed moderate toxicity between that of the more toxic graphene oxide and the relatively nontoxic MWCNTs. Environ Toxicol Chem 2016;35:2941-2947. © 2016 SETAC.