Biology subjects

Potokar, M.

Publications and source records attributed to Potokar, M..

3 recordsLinked to original sources

bioRxiv2026

β-Adrenergic inhibition of exocytotic surface deposition of MHCII molecules in reactive astrocytes is mediated by amisyn

Degeneration of the locus coeruleus, a noradrenergic nucleus, reduces noradrenaline bioavailability in the central nervous system and promotes neuroinflammation via reactive astrocytes, although the underlying mechanisms remain unclear. We investigated whether interferon-{gamma}-induced expression of major histocompatibility complex class II (MHCII), a marker of pro-inflammatory reactive astrocytes, is regulated by adrenergic receptors and amisyn. {beta}-Adrenergic, but not -adrenergic, stimulation increased cyclic adenosine monophosphate (cAMP) and reduced MHCII expression, as detected immunocytochemically, in human and rat astrocytes. {beta}-Adrenergic treatment altered transient exocytosis of lysosome-like vesicles, increasing event frequency and reducing fusion-pore conductance and dwell time, thereby limiting MHCII surface expression. Overexpression of wild-type amisyn inhibited surface expression of MHCII and the lysosomal marker CD63 and reduced fusion-pore conductance and dwell time. Conversely, amisyn knockdown enhanced full fusion exocytosis of larger vesicles and abolished {beta}-adrenergic effects, indicating that amisyn mediates {beta}-adrenergic inhibition of exocytosis and MHCII surface deposition.

neuroscience↗

bioRxiv2025

Ketamine inhibition of SARS-CoV-2 replication in astrocytes is associated with COVID-19 disease severity in a variant-dependent manner

Severe coronavirus infections, including SARS-CoV-2, can cause neurological symptoms, but the underlying neurotropic mechanisms are unclear. Experiments with SARS-CoV-2 variants B.1.258.17, B.1.1.7, and BA.5.3.2 (termed wild-type, alpha and omicron, respectively) revealed that human astrocytes, not neurons, support viral proliferation. During the COVID-19 pandemic, new virus variants exhibited milder disease progression. A retrospective study of patients with COVID-19 infected by wild-type or alpha variants was conducted to test whether ketamine, an anaesthetic that inhibits endocytosis, affects COVID-19. At admission, patients infected with the wild-type showed greater disease severity than alpha variant patients, but the disease course was similar. This may be due to distinct ketamine-mediated SARS-CoV-2 variant-dependent effects, revealing stronger ketamine inhibition of the wild-type variant than the alpha variant mediating astrocyte responses involving the expression of ACE2, a viral cell entry site, viral proteins RNA-dependent RNA polymerase and envelope protein-E in infected cells. Overexpression of SARS-CoV-2 protein 3a attenuated astroglial lysosomal traffic, and 3a and nsp6 differentially modulated lipid droplet accumulation and initiation of autophagy, where ketamine predominantly affected vesicle dynamics. In summary, human astrocytes, but not neurons, contribute to SARS-CoV-2 neurotropism, highlighting the potential benefits of ketamine treatment in coronavirus infections.

neuroscience↗

bioRxiv2025

Plectin Regulates Focal Adhesion Dynamics and Cytoskeletal Organization in Mouse Astrocytes: Implications for Reactive Astrogliosis

Reactive astrogliosis, a hallmark of central nervous system pathologies, involves cellular responses, including morphological remodelling and upregulation of intermediate filaments such as vimentin. These changes are driven by cytoskeletal dynamics and are mediated by focal adhesions (FAs). Our study identifies plectin, a versatile cytoskeletal linker protein, as a critical modulator of FA-associated processes in mouse astrocytes. We demonstrate that plectin localizes to astrocyte FAs, where it regulates their number, maturation, turnover, and the mobility of FA components. Plectin also polarizes within FAs, depending on their maturation state, and controls the recruitment of key cytoskeletal elements particularly vimentin. In plectin-deficient astrocytes, the vimentin network exhibits impaired connectivity, accompanied by altered viscoelastic properties of the cells. In a model of reactive astrocytes FA number and size were elevated along with the expression of plectin, highlighting involvement of plectin in pathological conditions.

neuroscience↗