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

Vrsnik, J.; Bozic, M.; Bunc, Z.; Potokar, M.; Sugiyama, K.; Dolinar, K.; Pirkmajer, S.; Anderluh, G.; Kreft, M.; Milosevic, I.; Jorgacevski, J.; Zorec, R.; Stenovec, M.

doi:10.64898/2026.08.19.745707

bioRxiv · 10.64898/2026.08.19.745707

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

Vrsnik, J.·Bozic, M.·Bunc, Z.·Potokar, M.·Sugiyama, K.·Dolinar, K.·Pirkmajer, S.·Anderluh, G.·Kreft, M.·Milosevic, I.·Jorgacevski, J.·Zorec, R.·Stenovec, M.

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Abstract

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.

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Vrsnik, J., Bozic, M., Bunc, Z., Potokar, M., Sugiyama, K., Dolinar, K., Pirkmajer, S., Anderluh, G., Kreft, M., Milosevic, I., Jorgacevski, J., Zorec, R., Stenovec, M.. 2026-08-24. β-Adrenergic inhibition of exocytotic surface deposition of MHCII molecules in reactive astrocytes is mediated by amisyn. https://doi.org/10.64898/2026.08.19.745707

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