Neurotoxic unc-8 mutants encode constitutively active DEG/ENaC channels that are blocked by divalent cations
Year: 2013
Type: article
Abstract: Ion channels of the DEG/ENaC family can induce neurodegeneration under conditions in which they become hyperactivated. The Caenorhabditis elegans DEG/ENaC channel MEC-4(d) encodes a mutant channel with a substitution in the pore domain that causes swelling and death of the six touch neurons in which it is expressed. Dominant mutations in the C. elegans DEG/ENaC channel subunit UNC-8 result in uncoordinated movement. Here we show that this unc-8 movement defect is correlated with the selective death of cholinergic motor neurons in the ventral nerve cord. Experiments in Xenopus laevis ooctyes confirm that these mutant proteins, UNC-8(G387E) and UNC-8(A586T), encode hyperactivated channels that are strongly inhibited by extracellular calcium and magnesium. Reduction of extracellular divalent cations exacerbates UNC-8(G387E) toxicity in oocytes. We suggest that inhibition by extracellular divalent cations limits UNC-8 toxicity and may contribute to the selective death of neurons that express UNC-8 in vivo.
Institutions: University of Miami, Vanderbilt University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Genes Controlling Assembly and Function of Serotonin Systems, Molelcular determinants of synaptic plasticity, G3590856881, G4376645998, Identification of Synaptic remodeling Genes in C. elegans, Molecular Genetics of Neural Specificity, Glia in Touch Sensation, G6121924544, Molecular Genetics of Synaptic Plasticity
OpenAlex ID: W2145223979