The pathogenic mechanism of cystic fibrosis (CF) includes the functional interaction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein with the epithelial sodium channel (ENaC). The reduction of ENaC activity may constitute a therapeutic option for CF. This hypothesis was ...
Subsequent identification of the TipE gene facilitated studies that demonstrated its NaV channel regulator activity by stimulating functional expression of Para in Xenopus oocytes, and established that TipE expression during pupal development rescued the paralysis phenotype in adult fruit flies [11]. More...
32 The heteromeric assembly of KCNQ2 and KCNQ3 encoded K+ channel subunits forms the M-channel.33 This mediates the slowly activating and non-inactivating M-current, which is an important regulator of neuronal excitability. The KCNQ2 and KCNQ3 mutations that cause BFNC occur either in the ...
Although palmitoylation is likely an important regulator of ion channel activity, evidence for the direct influence of palmitoylation on cellular excitability, and its potential involvement in cardiac sodium channelopathies, is lacking. In our study, we show that palmitoylation changes have profound impac...
Voltage gated sodium channels 1.2 and 1.7 (Nav1.2 and 1.7) contain PY motifs that interact with the WW domains of NEDD4 to result in down-regulation of the channel and reduced sodium channel activity in Xenopus oocytes (Fotia et al., 2004). 4.2 Growth factor signalling In the epidermal ...
decreased the stability and activity of the full-length form [45]. As such, common findings that support the role of a spliced form as a dominant negative expression regulator can be summarized as follows: a] the spliced form is non-functional [42], b] the frequency of the spliced form ...
MOG1 was initially identified as a protein that interacts with the small GTPase Ran involved in transport of macromolecules into and out of the nucleus. In addition, we have established that MOG1 interacts with the cardiac sodium channel Nav1.5 and regul
Defective regulatory interactions between the cystic fibrosis conductance regulator (CFTR) and the epithelial sodium channel (ENaC) have been implicated in the elevated Na+transport rates across cystic fibrosis airway epithelium. It has recently been proposed that ENaC downregulation by CFTR depends on th...
channel α subunit isoforms (Nav1.1, Nav1.2, Nav1.3, Nav1.4, Nav1.5, Nav1.6, Nav1.7, Nav1.8, and Nav1.9) and four types of β subunit isoforms (β1, β2, β3, and β4) have been identified in different human tissues [23,24] (Fig.1D). Generally, Nav channel α subunits are ...
collection of proteins, the ENaC regulatory complex (ERC) that contains proteins including SGK1, GILZ1, ERK, and Nedd4-2 that regulate channel stability in the membrane. The ERC under basal conditions contains several molecules including ERK and Nedd4-2 that inhibit ENaC activity. The C-...