Abstract
Epithelial Na+ Channel (ENaC) is critical for maintenance of sodium balance. Cortactin is a key signaling protein for many cellular processes, including direct interaction with F‐actin. In this study we have addressed the role of cortactin in mediating regulation of ENaC. As assessed by Western blotting, cortactin is highly expressed in mpkCCDc14, M‐1 and MDCK cells. Immunohistochemistry analysis showed localization of cortactin in the cortical collecting duct in Sprague‐Dawley rat kidneys. Co‐immunoprecipitation analysis revealed that cortactin directly interacts with ENaC subunits when co‐expressed in CHO cells. We have supported these data with fluorescent microscopy co‐localization approach and fluorescence correlation spectroscopy analysis. Coexpression of cortactin with ENaC decreased channel's activity as measured by patch‐clamp. Surprisingly, cortactin's dynamin‐binding Src homology 3 domain is not required for ENaC regulation. Similarly cortactin mutants with deleted phosphorylation domain, or lacking ability to bind F‐actin decrease ENaC current. However cortactin mutant unable to bind Arp2/3 complex does not influence ENaC activity. Thus, we conclude that cortactin decreases ENaC activity via Arp2/3 complex.Supported by AHA and ASN.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callSimilar Papers
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
