title: A Glial K/Cl Transporter Controls Neuronal Receptive Ending Shape by Chloride Inhibition of an rGC.
abstract: Neurons receive input from the outside world or from other neurons through neuronal receptive endings (NREs). Glia envelop NREs to create specialized microenvironments; however, glial functions at these sites are poorly understood. Here, we report a molecular mechanism by which glia control NRE shape and associated animal behavior. The C. elegans AMsh glial cell ensheathes the NREs of 12 neurons, including the thermosensory neuron AFD. KCC-3, a K/Cl transporter, localizes specifically to a glial microdomain surrounding AFD receptive ending microvilli, where it regulates K(+) and Cl(-) levels. We find that Cl(-) ions function as direct inhibitors of an NRE-localized receptor-guanylyl-cyclase, GCY-8, which synthesizes cyclic guanosine monophosphate (cGMP). High cGMP mediates the effects of glial KCC-3 on AFD shape by antagonizing the actin regulator WSP-1/NWASP. Components of this pathway are broadly expressed throughout the nervous system, suggesting that ionic regulation of the NRE microenvironment may be a conserved mechanism by which glia control neuron shape and function.
authors.affiliation: Laboratory of Developmental Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Aakanksha
authors.initials: A
authors.lastname: Singhvi
authors.affiliation: Department of Physiology, Weill Medical College, Cornell University, 1300 York Avenue, New York, NY 10065, USA.
authors.forename: Bingqian
authors.initials: B
authors.lastname: Liu
authors.affiliation: Laboratory of Developmental Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Friedman
authors.affiliation: Laboratory of Developmental Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Fong
authors.affiliation: Laboratory of Developmental Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Physiology, Weill Medical College, Cornell University, 1300 York Avenue, New York, NY 10065, USA.
authors.forename: Xin-Yun
authors.initials: XY
authors.lastname: Huang
authors.affiliation: Laboratory of Developmental Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Electronic address: shaham@rockefeller.edu.
authors.forename: Shai
authors.initials: S
authors.lastname: Shaham
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D006162:Guanylate Cyclase / Q000737:chemistry / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D000072417:Protein Domains; D011984:Sensory Receptor Cells / Q000378:metabolism*; D027981:Symporters / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013697:Thermosensing; D000096922:K Cl- Cotransporters
chemical_list: D029742:Caenorhabditis elegans Proteins; D006152:Cyclic GMP; D006162:Guanylate Cyclase; D011188:Potassium; D027981:Symporters; D000096922:K Cl- Cotransporters; C000611900:KCC-3 protein, C elegans; C532812:wsp-1 protein, C elegans; C511737:GCY-8 protein, C elegans