title: Enhanced locomotion caused by loss of the Drosophila DEG/ENaC protein Pickpocket1.
abstract: Coordination of rhythmic locomotion depends upon a precisely balanced interplay between central and peripheral control mechanisms. Although poorly understood, peripheral proprioceptive mechanosensory input is thought to provide information about body position for moment-to-moment modifications of central mechanisms mediating rhythmic motor output. Pickpocket1 (PPK1) is a Drosophila subunit of the epithelial sodium channel (ENaC) family displaying limited expression in multiple dendritic (md) sensory neurons tiling the larval body wall and a small number of bipolar neurons in the upper brain. ppk1 null mutant larvae had normal external touch sensation and md neuron morphology but displayed striking alterations in crawling behavior. Loss of PPK1 function caused an increase in crawling speed and an unusual straight path with decreased stops and turns relative to wild-type. This enhanced locomotion resulted from sustained peristaltic contraction wave cycling at higher frequency with a significant decrease in pause period between contraction cycles. The mutant phenotype was rescued by a wild-type PPK1 transgene and duplicated by expressing a ppk1RNAi transgene or a dominant-negative PPK1 isoform. These results demonstrate that the PPK1 channel plays an essential role in controlling rhythmic locomotion and provide a powerful genetic model system for further analysis of central and peripheral control mechanisms and their role in movement disorders.
authors.affiliation: Department of Physiology and Biophysics, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Ainsley
authors.forename: Janette M
authors.initials: JM
authors.lastname: Pettus
authors.forename: Dmitry
authors.initials: D
authors.lastname: Bosenko
authors.forename: Clare E
authors.initials: CE
authors.lastname: Gerstein
authors.forename: Natalya
authors.initials: N
authors.lastname: Zinkevich
authors.forename: Michael G
authors.initials: MG
authors.lastname: Anderson
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Adams
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welsh
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Johnson
mesh_terms: D000818:Animals; D015139:Blotting, Southern; D002874:Chromosome Mapping; D004330:Drosophila / Q000235:genetics* / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics*; D053503:Epithelial Sodium Channels; D005453:Fluorescence; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D007814:Larva / Q000502:physiology; D008124:Locomotion / Q000502:physiology*; D008959:Models, Neurological; D009119:Muscle Contraction / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology*; D015222:Sodium Channels / Q000235:genetics*; D019076:Transgenes / Q000235:genetics / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; D053503:Epithelial Sodium Channels; D015222:Sodium Channels; C532965:ppk protein, Drosophila