Epithelial UNC-23 limits mechanical stress to maintain glia-neuron architecture in C. elegans

Martin, Cecilia G.; Bent, James S.; Hill, Tyler; Topalidou, Irini; Singhvi, Aakanksha

doi:10.1016/j.devcel.2024.04.005

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2024

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Cited by 2 publications

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Glia in Invertebrate Models: Insights from Caenorhabditis elegans

Purice,

Severs,

Singhvi

2024

Advances in Neurobiology

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Glia in Invertebrate Models: Insights from Caenorhabditis elegans

Purice,

Severs,

Singhvi

2024

Advances in Neurobiology

View full text Add to dashboard Cite

Mechanical load conditions the spectrin network to ‘runon’ proteolysis and promotes early onset neurodegeneration

Malaiwong,

Dahse,

Lin

et al. 2024

Preprint

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The correct homeostasis of the neuronal cytoskeleton and its dynamics is important for health and disease. Forces constantly act on the neurons in our body, leading to subtle axonal deformations and length changes. The spectrin cytoskeleton is known as a key player that protects neurons against mechanical damage. How the spectrin cytoskeleton changes with age and how it influences mechanoprotection in aging animals is not well understood. Using an interdisciplinary approach, we show that age causes a loss of proprioception during the first few days of adulthood in Caenorhabditis (C.) elegans via spectrin unfolding, loss of mechanical tension and degradation of the spectrin cytoskeleton. Guided by a proteomic screen to identify potential spectrin binding partners, we found that this early-onset neurodegeneration can be suppressed in clp-1 Calpain mutants and by targeted expression of an engineered chaperone derived from human alphaB-crystallin. Our data suggest that the spectrin cytoskeleton is sensitized to proteolytic damage by calcium-sensitive proteases when mechanical stresses conspires with high-calcium concentrations as in proprioceptive signaling. These results may have implications for the etiology of diseases in which high calcium dynamics and mechanical stress coincide.

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Epithelial UNC-23 limits mechanical stress to maintain glia-neuron architecture in C. elegans

Cited by 2 publications

References 172 publications

Glia in Invertebrate Models: Insights from Caenorhabditis elegans

Glia in Invertebrate Models: Insights from Caenorhabditis elegans

Mechanical load conditions the spectrin network to ‘runon’ proteolysis and promotes early onset neurodegeneration

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