title: A glial DEG/ENaC channel functions with neuronal channel DEG-1 to mediate specific sensory functions in C. elegans.
abstract: Mammalian neuronal DEG/ENaC channels known as ASICs (acid-sensing ion channels) mediate sensory perception and memory formation. ASICS are closed at rest and are gated by protons. Members of the DEG/ENaC family expressed in epithelial tissues are called ENaCs and mediate Na(+) transport across epithelia. ENaCs exhibit constitutive activity and strict Na(+) selectivity. We report here the analysis of the first DEG/ENaC in Caenorhabditis elegans with functional features of ENaCs that is involved in sensory perception. ACD-1 (acid-sensitive channel, degenerin-like) is constitutively open and impermeable to Ca(2+), yet it is required with neuronal DEG/ENaC channel DEG-1 for acid avoidance and chemotaxis to the amino acid lysine. Surprisingly, we document that ACD-1 is required in glia rather than neurons to orchestrate sensory perception. We also report that ACD-1 is inhibited by extracellular and intracellular acidification and, based on the analysis of an acid-hypersensitive ACD-1 mutant, we propose a mechanism of action of ACD-1 in sensory responses based on its sensitivity to protons. Our findings suggest that channels with ACD-1 features may be expressed in mammalian glia and have important functions in controlling neuronal function.
authors.affiliation: Department of Physiology and Biophysics, Miller School of Medicine, University of Miami, Miami, FL, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Alfonso
authors.initials: A
authors.lastname: Apicella
authors.forename: Sun-Kyung
authors.initials: SK
authors.lastname: Lee
authors.forename: Marina
authors.initials: M
authors.lastname: Ezcurra
authors.forename: Robert D
authors.initials: RD
authors.lastname: Slone
authors.forename: Maya
authors.initials: M
authors.lastname: Goldmit
authors.forename: William R
authors.initials: WR
authors.lastname: Schafer
authors.forename: Shai
authors.initials: S
authors.lastname: Shaham
authors.forename: Monica
authors.initials: M
authors.lastname: Driscoll
authors.forename: Laura
authors.initials: L
authors.lastname: Bianchi
mesh_terms: D062565:Acid Sensing Ion Channels; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010465:Perception; D010802:Phylogeny; D011522:Protons; D017386:Sequence Homology, Amino Acid; D015222:Sodium Channels / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: C532398:ACD-1 protein, C elegans; D062565:Acid Sensing Ion Channels; D029742:Caenorhabditis elegans Proteins; C094927:Deg-1 protein, C elegans; D053503:Epithelial Sodium Channels; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011522:Protons; D015222:Sodium Channels; D002118:Calcium