Publications by authors named "Margherita Farina"
Proteostasis is essential for cellular survival and particularly important for highly specialised post-mitotic cells such as neurons. Transient reduction in protein synthesis by protein kinase R-like endoplasmic reticulum (ER) kinase (PERK)-mediated phosphorylation of eukaryotic translation initiation factor 2α (p-eIF2α) is a major proteostatic survival response during ER stress. Paradoxically, neurons are remarkably tolerant to PERK dysfunction, which suggests the existence of cell type-specific mechanisms that secure proteostatic stress resilience.
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- Research found that MUNC18-1 is essential for DCV exocytosis in CNS neurons, while other SM proteins (MUNC18-2 and MUNC18-3) do not support this function.
- Impaired neuropeptide secretion due to reduced MUNC18-1 expression may contribute to behavioral and developmental issues seen in heterozygous mice, which serve as a model for human STXBP1 syndrome.
Neuropeptides are essential signaling molecules transported and secreted by dense-core vesicles (DCVs), but the number of DCVs available for secretion, their subcellular distribution, and release probability are unknown. Here, we quantified DCV pool sizes in three types of mammalian CNS neurons and Super-resolution and electron microscopy reveal a total pool of 1,400-18,000 DCVs, correlating with neurite length. Excitatory hippocampal and inhibitory striatal neurons have a similar DCV density, and thalamo-cortical axons have a slightly higher density.
View Article and Find Full Text PDFNeuropeptides released from dense-core vesicles (DCVs) modulate neuronal activity, but the molecules driving DCV secretion in mammalian neurons are largely unknown. We studied the role of calcium-activator protein for secretion (CAPS) proteins in neuronal DCV secretion at single vesicle resolution. Endogenous CAPS-1 co-localized with synaptic markers but was not enriched at every synapse.
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- Neuronal dense-core vesicles (DCVs) are essential for brain development and function, but how they are released is not well understood.
- Researchers studied the release of DCVs in hippocampal neurons, finding that they mainly fuse at synaptic terminals but can also fuse at extrasynaptic sites following prolonged stimulation.
- In neurons lacking Munc13-1/2, synaptic DCV release was reduced but still possible; however, overexpressing Munc13-1 enhanced extrasynaptic DCV release without needing prolonged stimulation, showing Munc13-1/2 support DCV fusion but aren't absolutely necessary for their release.