ATPase N-ethylmaleimide-sensitive Fusion Protein: A Novel Key Player for Causing Spontaneous Network Excitation in Human Temporal Lobe Epilepsy

Herold, Christina; Bidmon, Hans‐Jürgen; Pannek, H. W.; Hans, Volkmar; Gorji, Ali; Speckmann, Erwin‐Josef; Zilles, Karl

doi:10.1016/j.neuroscience.2017.12.013

Cited by 4 publications

(4 citation statements)

References 57 publications

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“…Genome‐wide association studies significantly link MAPT and NSF to general cognitive function (Savage et al , 2018). Elevated synaptic NSF and AMPARs were linked to spontaneous spike‐wave formation in temporal lobe epilepsy (Herold et al , 2018). Tau is required for hyperexcitability in mouse models of epilepsy and stroke (Bi et al , 2017).…”

Section: Discussionmentioning

confidence: 99%

Tau target identification reveals NSF‐dependent effects on AMPA receptor trafficking and memory formation

et al. 2022

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Microtubule‐associated protein tau is a central factor in Alzheimer's disease and other tauopathies. However, the physiological functions of tau are unclear. Here, we used proximity‐labelling proteomics to chart tau interactomes in primary neurons and mouse brains in vivo. Tau interactors map onto pathways of cytoskeletal, synaptic vesicle and postsynaptic receptor regulation and show significant enrichment for Parkinson's, Alzheimer's and prion disease. We find that tau interacts with and dose‐dependently reduces the activity of N‐ethylmaleimide sensitive fusion protein (NSF), a vesicular ATPase essential for AMPA‐type glutamate receptor (AMPAR) trafficking. Tau‐deficient (tau−/−) neurons showed mislocalised expression of NSF and enhanced synaptic AMPAR surface levels, reversible through the expression of human tau or inhibition of NSF. Consequently, enhanced AMPAR‐mediated associative and object recognition memory in tau−/− mice is suppressed by both hippocampal tau and infusion with an NSF‐inhibiting peptide. Pathologic mutant tau from mouse models or Alzheimer's disease significantly enhances NSF inhibition. Our results map neuronal tau interactomes and delineate a functional link of tau with NSF in plasticity‐associated AMPAR‐trafficking and memory.

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Section: Discussionmentioning

confidence: 99%

Tau target identification reveals NSF‐dependent effects on AMPA receptor trafficking and memory formation

et al. 2022

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Section: Introductionmentioning

confidence: 99%

“…Additional glutamatergic inputs reach the hippocampus from the thalamus and the amygdala and GABAergic inputs reach the hippocampal subdivisions by further GABAergic interneurons (Buhl & Whittington, 2007; Klausberger & Somogyi, 2008). Regarding both systems, synaptic activity is differentially modulated by binding to specific receptor subtypes, co‐modulators of synaptic transmission and receptor cross‐talks that in turn lead to complex functional contributions (Duman et al, 2019; Duszkiewicz, McNamara, Takeuchi, & Genzel, 2019; Herold et al, 2018). For one example, both, glutamatergic NMDA and AMPA receptors are particularly involved in long‐term potentiation during memory formation (Collingridge, Kehl, & McLennan, 1983; R. G. Morris, Anderson, Lynch, & Baudry, 1986; Tsien, Huerta, & Tonegawa, 1996) and both receptor types also modulate hippocampal place cell activity that have been shown to increase place field size gradually from dorsal to ventral (Jung, Wiener, & McNaughton, 1994; Kjelstrup et al, 2008; Maurer, Vanrhoads, Sutherland, Lipa, & McNaughton, 2005).…”

Section: Introductionmentioning

confidence: 99%

New boundaries and dissociation of the mouse hippocampus along the dorsal‐ventral axis based on glutamatergic, GABAergic and catecholaminergic receptor densities

et al. 2020

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In rodents, gene-expression, neuronal tuning, connectivity and neurogenesis studies have postulated that the dorsal, the intermediate and the ventral hippocampal formation (HF) are distinct entities. These findings are underpinned by behavioral studies showing a dissociable role of dorsal and ventral HF in learning, memory, stress and emotional processing. However, up to now, the molecular basis of such differences in relation to discrete boundaries is largely unknown. Therefore, we analyzed binding site densities for glutamatergic AMPA, NMDA, kainate and mGluR 2/3 , GABAergic GABA A (including benzodiazepine binding sites), GABA B , dopaminergic D 1/5 and noradrenergic α 1 and α 2 receptors as key modulators for signal transmission in hippocampal functions, using quantitative in vitro receptor autoradiography along the dorsal-ventral axis of the mouse HF. Beside general different receptor profiles of the dentate gyrus (DG) and Cornu Ammonis fields (CA1, CA2, CA3, CA4/hilus), we detected substantial differences between dorsal, intermediate and ventral subdivisions and individual layers for all investigated receptor types, except GABA B. For example, striking higher densities of α 2 receptors were detected in the ventral DG, while the dorsal DG possesses higher numbers of kainate, NMDA, GABA A and D 1/5 receptors. CA1 dorsal and intermediate subdivisions showed higher AMPA, NMDA, mGluR 2/3 , GABA A , D 1/5 receptors, while kainate receptors are higher expressed in ventral CA1, and noradrenergic α 1 and α 2 receptors in the intermediate region of CA1. CA2 dorsal was distinguished by higher kainate, α 1 and α 2 receptors in the intermediate region, while CA3 showed a more complex dissociation. Our findings resulted not only in a clear segmentation of the mouse hippocampus along the dorsal-ventral axis, but also provides insights into the neurochemical basis and likely associated physiological processes in hippocampal functions. Therein, the presented data has a high impact for future studies modeling and investigating dorsal, intermediate and ventral hippocampal dysfunction in relation to neurodegenerative diseases or psychiatric disorders.

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“…This present study uncovered a previously unknown interaction of PRG-1 with NSF in hippocampus, and further dissected the role of PRG-1/NSF interaction in modulating RNS-induced impairments. NSF, iScience Article encoded by spontaneous recurrent epilepsy-related gene-1 (ERG1), is an ATPase known to play a key role in the release, docking, and fusion of synaptic vesicles, in addition to regulating the sorting, transport, and interaction of various neurotransmitter receptors on the postsynaptic membrane (Herold et al, 2018). ATP exerts multiple effects on synaptic plasticity and neuroglia interactions, as well as in mood disorders (Ma et al, 2018).…”

Section: Ll Open Accessmentioning

confidence: 99%

PRG-1 prevents neonatal stimuli-induced persistent hyperalgesia and memory dysfunction via NSF/Glu/GluR2 signaling

Liu¹,

Li²,

Zhang³

et al. 2022

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ATPase N-ethylmaleimide-sensitive Fusion Protein: A Novel Key Player for Causing Spontaneous Network Excitation in Human Temporal Lobe Epilepsy

Cited by 4 publications

References 57 publications

Tau target identification reveals NSF‐dependent effects on AMPA receptor trafficking and memory formation

Tau target identification reveals NSF‐dependent effects on AMPA receptor trafficking and memory formation

New boundaries and dissociation of the mouse hippocampus along the dorsal‐ventral axis based on glutamatergic, GABAergic and catecholaminergic receptor densities

PRG-1 prevents neonatal stimuli-induced persistent hyperalgesia and memory dysfunction via NSF/Glu/GluR2 signaling

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