Work

Primary cilia mediate specific neuron-glia attachments in C. elegans through the secreted protein BUG-1

Year: 2026

Type: article

Abstract: Primary cilia are signaling hubs that influence nearly every aspect of cell physiology. Neuronal primary cilia were recently found to form extensive attachments to glia in the mammalian brain, but it is not known how these attachments form or what functions they serve. Defects in cilia cause profound neurological disorders, highlighting the importance of understanding the specialized functions of neuronal cilia. Here, we use a genetic screen in Caenorhabditis elegans to determine how a stereotyped cilia-glia attachment forms and how the attachment affects ciliary calcium signaling. We find that two sensory neurons (URX and BAG) use their cilia to attach to a specific glial partner (ILsoL/R). This attachment requires BUG-1, a large secreted protein that localizes precisely to the cilia-glia attachment site. In the absence of BUG-1, neuronal cilia are present but always fail to attach to the glial cell. As a result, the URX cilia do not undergo activity-dependent remodeling seen in wild-type neurons and the BAG cilia exhibit reduced sensory stimulus-evoked calcium entry and defects in calcium clearance. Our work shows that cilia can select specific glial partners for attachment, identifies a novel protein that mediates these attachments, and demonstrates the functional consequences of loss of cilia-glia attachment on neuronal signaling. We propose that neuronal primary cilia act not only as antennae to receive long-range signals but also as points of close-range cell-cell contact, through which glia could modulate neuronal signaling.

Source: Current Biology

DOI: 10.1016/j.cub.2026.10.003