RRC ID 59472
Author Coakley S, Ritchie FK, Galbraith KM, Hilliard MA.
Title Epidermal control of axonal attachment via β-spectrin and the GTPase-activating protein TBC-10 prevents axonal degeneration.
Journal Nat Commun
Abstract Neurons are subjected to strain due to body movement and their location within organs and tissues. However, how they withstand these forces over the lifetime of an organism is still poorly understood. Here, focusing on touch receptor neuron-epidermis interactions using Caenorhabditis elegans as a model system, we show that UNC-70/β-spectrin and TBC-10, a conserved GTPase-activating protein, function non-cell-autonomously within the epidermis to dynamically maintain attachment of the axon. We reveal that, in response to strain, UNC-70/β-spectrin and TBC-10 stabilize trans-epidermal hemidesmosome attachment structures which otherwise become lost, causing axonal breakage and degeneration. Furthermore, we show that TBC-10 regulates axonal attachment and maintenance by inactivating RAB-35, and reveal functional conservation of these molecules with their vertebrate orthologs. Finally, we demonstrate that β-spectrin functions in this context non-cell-autonomously. We propose a model in which mechanically resistant epidermal attachment structures are maintained by UNC-70/β-spectrin and TBC-10 during movement, preventing axonal detachment and degeneration.
Volume 11(1)
Pages 133
Published 2020-1-9
DOI 10.1038/s41467-019-13795-x
PII 10.1038/s41467-019-13795-x
PMID 31919407
PMC PMC6952388
MeSH Animals Axons / physiology* Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism* Cytoskeleton / physiology Epidermis / metabolism GTPase-Activating Proteins / metabolism* Hemidesmosomes / metabolism Spectrin / metabolism* Stress, Physiological / physiology* rab GTP-Binding Proteins / metabolism
IF 11.878
Times Cited 0
C.elegans tm2790 tm2907