Fig. 3.

Huwe1 regulates inhibitory neurotransmission. a Schematic of a C. elegans motor circuit showing that EEL-1/HUWE1 is expressed in excitatory cholinergic and inhibitory GABAergic motor neurons, but preferentially affects GABAergic transmission. EEL-1 forms a complex with OGT-1 and functions parallel to OGT-1 to regulate GABA neuron function. b Schematic of excitatory and inhibitory connections to a mouse dorsal horn neuron in the spinal cord. Normally (left), glycinergic transmission inhibits excitatory input to nociceptive neurons. After peripheral tissue damage (right), Huwe1 is required to reduce glycinergic inhibitory transmission that stimulates inflammatory pain. This requires NMDAR-dependent recruitment of Huwe1, which ubiquitinates GlyRα1 and triggers GlyRα1 endocytosis (right). For A, diagram originally published in the Journal of Biological Chemistry. Giles, Desbois, Opperman, Tavora, Maroni, Grill. J. Biol. Chem. 2019; 294: 6843–6856.© Giles, Desbois, Opperman, Tavora, Maroni, Grill