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

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. [Display omitted] •Glia discriminate among their associated neurons•Glia impact neuron shape/function by control of the neuronal ionic microenvironment•Chloride ions are inhibitory ligands of receptor guanylyl cyclases•cGMP inhibits sensory microvilli shape through WASP and independent of CNG channels Glia regulate the shape and function of restricted subsets of the neurons they ensheath by modulating the ionic microenvironment, thereby controlling specific aspects of animal behavior.