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COMMD10: A Novel Regulator Of ENaC Trafficking?
Author(s) -
Ware Adam,
Burstein Ezra,
McDonald Fiona
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1223.8
Subject(s) - epithelial sodium channel , microbiology and biotechnology , heterotrimeric g protein , nav1.5 , transport protein , reabsorption , gene knockdown , chemistry , renal sodium reabsorption , regulator of g protein signaling , protein subunit , apical membrane , regulator , g protein , sodium channel , biology , signal transduction , gtpase activating protein , kidney , biochemistry , membrane , endocrinology , sodium , gene , organic chemistry
The Epithelial Sodium channel (ENaC) is a heterotrimeric (consisting of one α, one β and one γ subunit) Na + channel and is located at the apical membrane of polarised epithelia, such as the distal kidney, lung and colon, where it has an important role in Na + reabsorption for maintenance of total body Na + , blood pressure and blood volume. ENaC's trafficking to and from the plasma membrane is a highly regulated but not completely understood process. One protein that has been identified as playing a role in ENaC trafficking is COMMD1, a member of the COMMD (Copper Metabolism Murr1 domain containing) family of proteins. The other family members however have not been as extensively studied, including COMMD10, the focus of our study. Preliminary data has suggested an interaction between COMMD10 and Arf1 (a small GTP binding protein with various functions throughout the trafficking pathway) which suggests a role for COMMD10 in protein trafficking. Our work aims to investigate whether COMMD10 is a novel regulator of the protein trafficking pathway, and thus, whether it is involved in ENaC trafficking to and/or from the plasma membrane. A stable COMMD10 knockdown reduces amiloride‐sensitive short circuit current in αβγ‐ENaC transfected FRT epithelia. A COMMD10 knockdown reduces protein expression of some proteins (Vps35 and COMMD1) involved in the retromer complex (a complex implicated in the recycling of ENaC back to the plasma membrane). These results suggest that when COMMD10 is knocked down ENaC trafficking is disrupted. We have also identified that COMMD10 and Arf1, both in its wild‐type form as well as constitutively active and constitutively inactive forms, co‐localise. However, no co‐localisation was observed between COMMD10 and other Arf family members (Arf4 and Arf5) suggesting an Arf1 specific function for COMMD10. Using a cell‐line in which COMMD10 is stabily knocked down we have identified a change in localisation of the active form of Arf1, that when taken with the other results suggests a role for COMMD10 in the protein trafficking pathway. Support or Funding Information University of Otago PhD Scholarship