Glia actively sculpt sensory neurons by controlled phagocytosis to tune animal behavior

Abstract

Glia in the central nervous system engulf neuron fragments during synapse remodeling and recycling of photoreceptor outer-segments. Whether glia passively clear shed neuronal debris, or actively remove neuron fragments is unknown. How pruning of single-neuron endings impacts animal behavior is also unclear. Here we report that adult C. elegans AMsh glia engulf sensory endings of the AFD thermosensory neuron. Engulfment is regulated by temperature, AFD’s sensory input, and tracks AFD activity. Phosphatidylserine (PS) flippase TAT-1/ATP8A, functions with glial PS-receptor PSR-1/PSR and PAT-2/α-integrin to initiate engulfment. Glial CED-10/Rac1 GTPase, acting through a conserved GEF complex, executes phagocytosis using the actin-remodeler WSP-1/nWASp and the membrane-sealing factor EFF-1 fusogen. CED-10 levels determine engulfment rates, and engulfment-defective mutants exhibit altered AFD-ending shape and thermosensory behavior. Our findings reveal a molecular pathway underpinning glia-dependent phagocytosis in a peripheral sense-organ, and demonstrate that glia actively engulf neuron-fragments, with profound consequences on neuron shape and animal behavior.

Engulfed by Glia: Glial Pruning in Development, Function, and Injury across Species

“…Some of these proteins are orthologs of molecules previously implicated in glial engulfment in Drosophila (CED-12/ELMO, CED-10/Rac1 GTPase) and mammalian retina (Rac1 GTPase) (Kevany and Palczewski, 2010;Freeman, 2015) (Table 1). In addition, we uncovered two novel mediators for glial engulfment, including a PS receptor and a regulator of PS exposure (Raiders et al, 2020). These findings underscore the analogous molecular mechanisms of glial engulfment across species (C. elegans to human), systems (CNS/PNS), and context (development, injury, function), and they highlight the speed and precision this experimental setting affords.…”

“…In monitoring AMsh glia-AFD contact zones in vivo using transgenically labeled animals, we serendipitously observed labeled AFD puncta that were discontinuous with the AFD cell body and within AMsh glia. Subsequent validation studies confirmed that these puncta indeed reflect fragments of AFD ending engulfed by the AMsh glia (Raiders et al, 2020). Thus, engulfment is another glial function conserved in C. elegans.…”

“…(2) AMsh glia-regulated engulfment dynamically modifies AFD neuron shape and tunes thermotaxis behavior of adult animals (Raiders et al, 2020). Together, these studies provide an explicit demonstration that engulfment of a single neuron by a single glia directly modulates neuron shape and animal behavior.…”