The scaffold protein IQGAP1 regulates the epithelial Na+ channel

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The epithelial Na + channel (ENaC), by mediating the flow of Na + ions across biological membranes, plays a key role in the regulation of Na + and water absorption in several human epithelia.IQGAP1 is a scaffold protein that mediates diverse cellular processes including intracellular signaling and trafficking.In this study, we establish that IQGAP1 binds to ENaC and regulates its functions.We observed that IQGAP1 co-resides with aquaporin 2 in ENaCexpressing principal cells of the distal nephron of mouse kidney.We showed that purified IQGAP1 pulls down the α-, β-, and γ-subunits of ENaC.We demonstrated that endogenous IQGAP1 co-immunoprecipitates with ENaC subunits in MDCK cell lysates.Functionally, coexpression of IQGAP1 with ENaC in Xenopus oocytes reduces ENaC surface abundance and amiloride-sensitive Na + transport activity.Together, our data indicate that IQGAP1 binds to ENaC, which likely influences channel trafficking to regulate its cell surface abundance and Na + transport function.More broadly, these observations suggest new physiological roles for IQGAP1 in Na + and water absorption in epithelium.

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