Biology subjects

de Faria, O.

Publications and source records attributed to de Faria, O..

3 recordsLinked to original sources

bioRxiv2026

Myelin basic protein is an RNA chaperone in microglial nuclear retro-transport

CNS oligodendrocytes generate myelin, an RNA-containing proteolipid substance that enhances axonal transmission. In multiple sclerosis (MS), myelin debris is phagocytosed by microglia (MG), and prior studies have detected myelin-derived mRNA in MG nuclei, suggesting a retrograde transport pathway. We report myelin basic protein (MBP) is a nucleic acid-binding and trafficking protein. We found that retro-transport of myelin RNA into the MG nucleus was phagocytosis and importin-dependent. Transcriptomic and proteomic analyses of MG nuclei revealed enrichment of myelin mRNAs and proteins, with MBP singularly detected in soluble and chromatin-associated fractions. MBP bound mRNA with high affinity (Kd {approx} 0.30 nM) and was sufficient to facilitate MG RNA nuclear import in vitro and in vivo. Functionally, MBP mediated the delivery of small interfering RNAs for targeted knockdown of toll-like receptor 4. These findings indicate MBP as an RNA-binding protein capable of MG nuclear import, providing insight into neuroinflammatory pathology of MS.

neuroscience↗

bioRxiv2025

Constitutive DREADD signalling modulates oligodendrocyte precursor cell bioelectrical membrane properties and fate

Oligodendrocyte precursor cells (OPCs) are small cells in the central nervous system that proliferate and differentiate into myelinating oligodendrocytes throughout life, allowing for myelin plasticity and repair. G protein-coupled neuromodulator receptors can regulate OPC fate, but the role of individual G protein families is unclear. Here, we use chemogenetics to directly investigate the role of Gq and Gi proteins in OPC fate. We find that expressing the DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) hM3Dq or hM4Di in OPCs without activating them with designer agonists induces constitutive G protein signalling, which alters bioelectrical membrane properties such as voltage-gated ion channels and glutamate receptors in OPCs. Further, we find that hM3Dq or hM4Di expression alone modulates OPC fate, increasing or decreasing differentiation, respectively, suggesting that directly targeting G protein signalling can be used to bidirectionally regulate differentiation. Importantly, our data raise a note of caution regarding the use of DREADDs in both excitable and non-excitable small cells. SIGNIFICANCE STATEMENTDesigner Receptors Exclusively Activated by Designer Drugs (DREADDs) are widely used to manipulate neuronal excitability. Their use in other neural cell types is rapidly increasing; however, DREADDs have not been thoroughly characterized in non-neuronal cells. Here, we show that when expressed in small excitable cells like oligodendrocyte precursor cells, DREADDs are constitutively active, unlike in excitatory neurons. This constitutive DREADD signalling alters cell fate and bioelectrical membrane properties like voltage-gated ion channels and glutamate receptors. Our data highlight that constitutive DREADD activity represents a significant confound that needs to be considered and controlled for when expressing DREADDs in small cells, and demonstrate that G protein signalling is a potent regulator of OPC fate, with a potential for therapeutic implications.

neuroscience↗

bioRxiv2020

Paranode stability requires UNC5B expression by oligodendrocytes

In the mature CNS, netrin-1 is expressed by neurons and oligodendrocytes and implicated in the stability of axo-oligodendroglial paranodal junctions. Here we report that the netrin receptor UNC5B is highly expressed by mature oligodendrocytes and enriched at paranodes. We demonstrate that paranodes become disorganized following conditional deletion of UNC5B in oligodendrocytes, with disruption of the interface between glial loops and detachment of loops from the axon. As a result, Caspr1 and Kv1.1 disperse along the axon, internodes fail to lengthen and compact myelin periodicity is reduced. Paranodal and axoglial domain disorganization progressively worsens and a delay in motor learning develops in aged mice lacking oligodendroglial UNC5B. Altered glial loop ultrastructure and reduced levels of claudin-11 and JAM-C tight junction proteins support the conclusion that disruption of autotypic junctions between paranodal loops underlies paranode disorganization. Our findings reveal an essential contribution of oligodendroglial UNC5B at paranodes that is required for the stability of mature myelin.

neuroscience↗