A Glial K/Cl Transporter Controls Neuronal Receptive Ending Shape by Chloride Inhibition of an rGC

Cell. 2016 May 5;165(4):936-48. doi: 10.1016/j.cell.2016.03.026. Epub 2016 Apr 7.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / metabolism
  • Cyclic GMP / metabolism
  • Guanylate Cyclase / chemistry
  • Guanylate Cyclase / metabolism
  • Neuroglia / metabolism*
  • Potassium / metabolism
  • Protein Domains
  • Sensory Receptor Cells / metabolism*
  • Symporters / chemistry
  • Symporters / genetics
  • Symporters / metabolism*
  • Thermosensing

Substances

  • Caenorhabditis elegans Proteins
  • KCC-3 protein, C elegans
  • Symporters
  • potassium-chloride symporters
  • wsp-1 protein, C elegans
  • GCY-8 protein, C elegans
  • Guanylate Cyclase
  • Cyclic GMP
  • Potassium