Biology subjects

Buonarati, O. R.

Publications and source records attributed to Buonarati, O. R..

3 recordsLinked to original sources

bioRxiv2025

Oxygen/glucose-deprivation causes long-term impairment of synaptic CaMKII movement

Learning and memory are thought to require hippocampal long-term potentiation (LTP), a form of synaptic plasticity that is persistently impaired after cerebral ischemia and that requires movement of the Ca2+/calmodulin-dependent protein kinase II (CaMKII) to excitatory synapses. We show here that oxygen/glucose-deprivation (OGD) in cultures hippocampal neurons causes a long-lasting impairment of CaMKII movement. Notably, CaMKII inhibition at 30 min after onset of OGD prevented the impairment in CaMKII movement. Thus, CaMKII mediates both, LTP mechanisms and their ischemia-induced impairment. These findings provide a mechanism by which ischemic conditions can impair LTP and explain how CaMKII inhibition after cerebral ischemia can prevent these LTP impairments.

neuroscience↗

bioRxiv2022

CaMKII binding to GluN2B flips a β-adrenergic switch from synaptic depression to potentiation

Learning, memory and cognition are thought to require forms of synaptic plasticity such as hippocampal long-term potentiation and depression (LTP and LTD), and such plasticity can be modulated by {beta}-adrenergic stimulation with isoproterenol or norepinephrine. For instance, LTP versus LTD is induced by high-versus low-frequency stimulation (HFS versus LFS) but, stimulating {beta}-adrenergic receptors ({beta}ARs) enables LTP induction also by LFS. In contrast to HFS-LTP, such {beta}AR-LTP requires signaling by L-type voltage-gated Ca2+-channels, not NMDA-type glutamate receptors (NMDARs). Surprisingly, we found that {beta}AR-LTP still required a non-ionotropic NMDAR function: the stimulus-induced binding of the Ca2+/calmodulin-dependent protein kinase II (CaMKII) that mediates CaMKII movement to excitatory synapses. In hippocampal neurons, {beta}-adrenergic stimulation with isoproterenol transformed LTD-type CaMKII movement to LTP-type movement, resulting in CaMKII movement to excitatory instead of inhibitory synapses. Additionally, isoproterenol enabled induction of a major cell-biological feature of LTP in response to LTD stimuli: increased SEP-GluA1 surface expression. Like for the {beta}AR-LTP in hippocampal slices, the effects of isoproterenol on CaMKII movement and SEP-GluA1 surface expression involved L-type Ca2+-channels. Taken together, these results indicate that isoproterenol transforms LTD stimuli to LTP signals by switching CaMKII movement and GluN2B binding to LTP mode. One Sentence SummaryBuonarati et al. show that {beta}-adrenergic stimulation enables LTP induction in response to LTD stimuli by switching synaptic CaMKII movement to LTP mode.

neuroscience↗

bioRxiv2021

Conserved and divergent features of neuronal CaMKII holoenzyme structure, function, and high-order assembly

Neuronal CaMKII holoenzymes (- and {beta}-isoforms) enable molecular signal computation underlying learning and memory, but also mediate excitotoxic neuronal death. Here, we provide a comparative analysis of these signaling devices, using single particle EM in combination with biochemical and live-cell imaging studies. In the basal state, both isoforms assembled mainly as 12-mers (but also 14-mers, and even 16-mers for the {beta}-isoform). CaMKII and {beta}-isoforms adopted an ensemble of extended activatable states (with average radius of 12.6 versus 16.8 nm, respectively), characterized by multiple transient intra- and inter-holoenzyme interactions associated with distinct functional properties. The extended state of CaMKII{beta} allowed EM analysis to directly resolve intra-holoenzyme kinase-domain dimers that could enable the cooperative activation mechanism by calmodulin, which was found for both isoforms. Surprisingly, high-order CaMKII clustering mediated by inter-holoenzyme kinase-domain dimerization was reduced for the {beta} isoform for both basal and excitotoxicity-induced clusters, both in vitro and in neurons.

molecular biology↗