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Novel role of Rac1/WAVE signaling mechanism in regulation of the epithelial Na + channel (ENaC)
Author(s) -
Staruschenko Alexander,
Karpushev Alexey,
Levchenko Vladislav,
Ilatovskaya Daria V.,
Pavlov Tengis S.
Publication year - 2011
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.25.1_supplement.1039.1
Subject(s) - epithelial sodium channel , rac1 , channel (broadcasting) , mechanism (biology) , microbiology and biotechnology , chemistry , signal transduction , biology , physics , telecommunications , computer science , sodium , organic chemistry , quantum mechanics
ENaC is an essential channel responsible for Na + reabsorption in the ASDN. We have shown recently that small GTPase Rac1 increases ENaC activity, whereas Cdc42 fails to change channel activity. Here we tested whether Rac1 signaling plays a physiologic role in modulating ENaC in native tissue and polarized epithelial cells. We have found that Rac1 inhibitor NSC23766 markedly decreased ENaC activity in freshly isolated collecting ducts. Knockdown of Rac1 in native principal cells decreased ENaC‐mediated sodium reabsorption and the number of channels at the apical plasma membrane. Members of the Wiskott‐Aldrich syndrome protein (WASP) family play central roles in control of the actin cytoskeleton. N‐WASP binds Arp2/3 in response to Cdc42, whereas WAVE proteins are effectors of Rac1 activity. Using electrophysiological approaches we have shown that WAVE proteins significantly increase ENaC activity. Immunoblotting demonstrated the presence of WAVE1 and WAVE2 and absence of N‐WASP and WAVE3 in mpkCCD c14 and M‐1 principal cells. Immunohistochemistry analysis also detected only expression of WAVE1 and WAVE2 in the cortical collecting ducts in Sprague‐Dawley rat kidneys. Patch clamp analysis revealed that Rac1 and WAVE1/2 are parts of the same signaling with respect to activation of ENaC. Thus, our findings suggest that Rac1 is essential for ENaC activity and regulates the channel via WAVE proteins.