Temperature Regulates Astroglia Morphogenesis Through Thermosensory Circuitry in Caenorhabditis elegans

Glia, Год журнала: 2025, Номер unknown

Опубликована: Янв. 8, 2025

ABSTRACT Astrocytes are the most abundant type of macroglia in brain and play crucial roles regulating neural development functions. The diverse functions astrocytes largely determined by their morphology, which is regulated genetic environmental factors. However, whether how astrocyte morphology affected temperature remains unknown. Here we discovered that elevated cultivation (26°C) stimulates Caenorhabditis elegans ventral CEPsh glia endfoot extension during early developmental stages. This depends on activation glutamate AWC neurons, inhibit postsynaptic cholinergic AIY interneurons through glutamate‐gated chloride channels, GLC‐3 GLC‐4. In responding to thermosensory signal, guanyl‐nucleotide exchange factor EPHX‐1 Rho GTPase CDC‐42/Cdc42 facilitate via F‐actin assembly. study elucidates significant role circuitry morphogenesis underlying molecular mechanism.

Язык: Английский

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Remodeling of extracellular matrix collagen IV by MIG-6/papilin regulates neuronal architecture

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 10, 2025

Neuronal architecture established embryonically must persist lifelong to ensure normal brain function. However, little is understood about the mechanisms behind long-term maintenance of neuronal organization. To uncover mechanisms, we performed a suppressor screen in sax-7 / L1CAM mutants, which exhibit progressive disorganization with age. We identified conserved extracellular matrix protein MIG-6/papilin as key regulator maintenance. Combining incisive molecular genetics, structural predictions, vivo quantitative imaging, and cutting-edge Brillouin microscopy, show that remodels collagen IV, working concert secreted enzymes MIG-17/ADAMTS PXN-2/peroxidasin. This remodeling impacts tissue biomechanics ensures stability, even under increased mechanical stress. Our findings highlight an mechanism by supports integrity throughout life. work provides critical insights into basis sustaining offers foundation for understanding age-related neurodegenerative disorders.

Язык: Английский

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Mechanical load conditions the spectrin network to `run-on' proteolysis and promotes early onset neurodegeneration

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 4, 2024

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

Язык: Английский

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Glia in Invertebrate Models: Insights from Caenorhabditis elegans

Advances in neurobiology, Год журнала: 2024, Номер unknown, С. 19 - 49

Опубликована: Янв. 1, 2024

Язык: Английский

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