IGDB-2, an Ig/FNIII protein, binds the ion channel LGC-34 and controls sensory compartment morphogenesis in C. elegans

Abstract

Sensory organ glia surround neuronal receptive endings (NREs), forming a specialized compartment important for neuronal activity, and reminiscent of glia-ensheathed synapses in the central nervous system. We previously showed that DAF-6, a Patched-related protein, is required in glia of the C. elegans amphid sensory organ to restrict sensory compartment size. LIT-1, a Nemo-like kinase, and SNX-1, a retromer component, antagonize DAF-6 and promote compartment expansion. To further explore the machinery underlying compartment size control, we sought genes whose inactivation restores normal compartment size to daf-6 mutants. We found that mutations in igdb-2, encoding a single-pass transmembrane protein containing Ig-like and fibronectin type III domains, suppress daf-6 mutant defects. IGDB-2 acts in glia, where it localizes to glial membranes surrounding NREs, and, together with LIT-1 and SNX-1, regulates compartment morphogenesis. Immunoprecipitation followed by mass spectrometry demonstrates that IGDB-2 binds to LGC-34, a predicted ligand-gated ion channel, and lgc-34 mutations inhibit igdb-2 suppression of daf-6. Our findings reveal a novel membrane protein complex and suggest possible mechanisms for how sensory compartment size is controlled.

Morphogenesis of neurons and glia within an epithelium

“…The two glial cells, called the sheath and socket, each extend a single process to the nose where they form a tube-shaped pore through which most of the dendrites have direct access to the outside environment (Ward et al, 1975). The sheath completely wraps the dendrite endings, creating a local environment that can affect sensory function (Perens and Shaham, 2005;Bacaj et al, 2008;Wang et al, 2008;Oikonomou et al, 2011Oikonomou et al, , 2012Procko et al, 2011;Singhvi et al, 2016;Wallace et al, 2016;Wang et al, 2017), while the socket forms an opening continuous with the skin. Most of the dendrite endings protrude through this tube-shaped glial pore into the environment, and are decorated with cilia bearing receptors for specific smells, tastes or other stimuli (Bargmann, 2006).…”

Caenorhabditis elegans PTR/PTCHD PTR-18 promotes the clearance of extracellular hedgehog-related protein via endocytosis

“…In addition to their involvement in molting, the functions of few C. elegans ptr genes have been reported in detail. For instance, daf-6 is involved in the formation of the glial channel that surrounds the receptive endings of the sensory neurons and likely regulates vesicular transport [37][38][39][40]. ptr-24 has been proposed to act downstream of the hh-r gene, grl-21, to regulate mitochondrial fragmentation and lipid accumulation [41].…”

C. elegans as a model to study glial development

“…The exact mechanisms underlying this morphogenetic change are currently unclear, and future work will need to be done to learn more about these cells. [57,58]. The implication of retromer complex components suggests that vesicle trafficking may be a potential mechanism for controlling channel size.…”