Editors' ChoiceNeuroscience

Glia dictate neuronal morphology

Sci. Signal.  17 May 2016:
Vol. 9, Issue 428, pp. ec117
DOI: 10.1126/scisignal.aag1380

The AFD neuron is part of a thermotactic neural circuit in Caenorhabditis elegans that enables the animals to sense and migrate toward temperatures associated with past cultivation conditions. The receptive end of this neuron consists of microvilli and a single cilium. An AMsh glial cell surrounds this receptive end, as well as those of other neurons, such as the AWC neuron, which do not have this microvillar morphology. Singhvi et al. (see also Sun and Barres) found that microvillar extension required the increased Cl concentrations around the receptive end of the AFD neuron mediated by the K/Cl cotransporter KCC-3 in the AMsh glial cell. KCC-3 localized to the part of the AMsh cell surrounding the microvillus of the AFD neuron. Worms with an inactivating mutation in kcc-3 exhibited defects in thermotaxis and the AFD neuron lacked microvilli. However, the receptive end of the AWC neuron was unaffected by this inactivating mutation. Culturing the worms on plates supplemented with KCl or introducing an inactivating mutation in the gene encoding the receptor guanylyl cyclase GCY-8, an enzyme that produces cGMP and that had substantial ligand-independent basal activity, rescued the AFD morphology defect. The extracellular domain of GCY-8 contained a conserved Cl binding motif, and binding of Cl to this motif inhibited the basal activity of GCY-8. Increasing cGMP concentrations in the AFD neuron by overexpressing constitutively active human guanylyl cyclases or inactivating phosphodiesterase-encoding genes blocked microvillar extension. Overexpression of the actin regulator WSP-1 rescued formation of microvilli in worms with a gain-of-function mutation in gcy-8, suggesting inhibition of WSP-1 by cGMP prevents microvillar extension. Thus, by altering the extracellular ionic microenvironment, the AMsh glial cell affects the shape and function of the receptive end of the AFD neuron.

A. Singhvi, B. Liu, C. J. Friedman, J. Fong, Y. Lu, X.-Y. Huang, S. Shaham, A glial K/Cl transporter controls neuronal receptive ending shape by chloride inhibition of an rGC. Cell 165, 936–948 (2016). [PubMed]

L. O. Sun, B. A. Barres, Glia get neurons in shape. Cell 165, 775–776 (2016). [PubMed]