Premium
WAVE proteins mediate ENaC activity
Author(s) -
Karpushev Alexey V,
Levchenko Vladislav,
Staruschenko Alexander
Publication year - 2010
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.24.1_supplement.611.2
Subject(s) - epithelial sodium channel , rac1 , microbiology and biotechnology , wiskott–aldrich syndrome protein , biology , cdc42 , actin , gene isoform , reabsorption , cytoskeleton , actin cytoskeleton , chemistry , cell , gene , biochemistry , endocrinology , signal transduction , kidney , sodium , organic chemistry
The epithelial Na + channel (ENaC) is an essential channel responsible for Na + reabsorption. Similar to other ion channels, ENaC activity is regulated, in part, by cortical cytoskeleton. Members of the Wiskott‐Aldrich syndrome protein (WASP)/WAVE family (N‐WASP, WASP, and WAVE1, −2, −3 isoforms) activate Arp2/3‐mediated actin polymerization, leading to distinct downstream effects. N‐WASP inducibly binds Arp2/3 in response to Cdc42, whereas WAVE proteins constitutively interact with Arp2/3 and are effectors of Rac1 activity. Coexpression of Rac1 with ENaC markedly increased channel activity, whereas coexpression of Cdc42 failed to change ENaC activity. N‐WASP and all three isoforms of WAVE significantly increase ENaC activity when coexpressed in CHO cells. However, wiskostatin, an inhibitor of N‐WASP did not effect ENaC activity in cells expressing the channel alone and coexpressed with either N‐WASP or WAVE1. Similarly, wiskostatin had no effect on Na + reabsorption across mpkCCD c14 principal cell monolayers. Immunoblotting demonstrated the presence of WAVE1 and WAVE2 and absence of N‐WASP and WAVE3 in mpkCCD c14 and M‐1 cells. Immunohistochemistry analysis also revealed localization of only WAVE isoforms in the cortical collecting duct in Sprague‐Dawley rat kidneys in vivo . Thus, our findings suggest that WAVE proteins mediate ENaC activity via interaction with Rac1. Supported by AHA and ASN.