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Publication
Glial Expression of the Caenorhabditis elegans Gene swip-10 Supports Glutamate
Dependent Control of Extrasynaptic Dopamine Signaling.
Authors Hardaway JA, Sturgeon SM, Snarrenberg CL, Li Z, Xu XZ, Bermingham DP, Odiase P,
Spencer WC, Miller DM, Carvelli L, Hardie SL, Blakely RD
Submitted By Submitted Externally on 10/1/2015
Status Published
Journal The Journal of neuroscience : the official journal of the Society for Neuroscience
Year 2015
Date Published 6/1/2015
Volume : Pages 35 : 9409 - 23
PubMed Reference 26109664
Abstract Glial cells play a critical role in shaping neuronal development, structure, and
function. In a screen for Caenorhabditis elegans mutants that display dopamine
(DA)-dependent, Swimming-Induced Paralysis (Swip), we identified a novel gene,
swip-10, the expression of which in glia is required to support normal swimming
behavior. swip-10 mutants display reduced locomotion rates on plates, consistent
with our findings of elevated rates of presynaptic DA vesicle fusion using
fluorescence recovery after photobleaching. In addition, swip-10 mutants exhibit
elevated DA neuron excitability upon contact with food, as detected by in vivo
Ca(2+) monitoring, that can be rescued by glial expression of swip-10. Mammalian
glia exert powerful control of neuronal excitability via transporter-dependent
buffering of extracellular glutamate (Glu). Consistent with this idea, swip-10
paralysis was blunted in mutants deficient in either vesicular Glu release or
Glu receptor expression and could be phenocopied by mutations that disrupt the
function of plasma membrane Glu transporters, most noticeably glt-1, the
ortholog of mammalian astrocytic GLT1 (EAAT2). swip-10 encodes a protein
containing a highly conserved metallo-ß-lactamase domain, within which our
swip-10 mutations are located and where engineered mutations disrupt Swip
rescue. Sequence alignments identify the CNS-expressed gene MBLAC1 as a putative
mammalian ortholog. Together, our studies provide evidence of a novel pathway in
glial cells regulated by swip-10 that limits DA neuron excitability, DA
secretion, and DA-dependent behaviors through modulation of Glu signaling.




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