scholarly journals An essential postsynaptic role for the ubiquitin proteasome system in slow homeostatic synaptic plasticity in cultured hippocampal neurons

Neuroscience ◽  
2010 ◽  
Vol 171 (4) ◽  
pp. 1016-1031 ◽  
Author(s):  
S.K. Jakawich ◽  
R.M. Neely ◽  
S.N. Djakovic ◽  
G.N. Patrick ◽  
M.A. Sutton
Keyword(s):  
Synaptic Plasticity ◽  
Hippocampal Neurons ◽  
Ubiquitin Proteasome System ◽  
Homeostatic Synaptic Plasticity ◽  
Ubiquitin Proteasome ◽  
Cultured Hippocampal Neurons

scholarly journals Age-dependent glutamate induction of synaptic plasticity in cultured hippocampal neurons

2006 ◽  
Vol 13 (6) ◽  
pp. 719-727 ◽  
Author(s):  
S. Sapoznik ◽  
M. Ivenshitz ◽  
M. Segal
Keyword(s):  
Synaptic Plasticity ◽  
Hippocampal Neurons ◽  
Age Dependent ◽  
Cultured Hippocampal Neurons

scholarly journals Pregnenolone Sulfate Activates NMDA Receptor Channels

2013 ◽  
pp. 731-736 ◽  
Author(s):  
E. ADAMUSOVÁ ◽  
O. CAIS ◽  
V. VYKLICKÝ ◽  
E. KUDOVÁ ◽  
H. CHODOUNSKÁ ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Ion Channels ◽  
Nmda Receptor ◽  
Calcium Signaling ◽  
Hippocampal Neurons ◽  
Hek293 Cells ◽  
Independent Effect ◽  
Pregnenolone Sulfate ◽  
Specific Manner ◽  
Cultured Hippocampal Neurons

Pregnenolone sulfate (PS), an endogenously occurring neurosteroid, has been shown to modulate the activity of several neurotransmitter-gated channels, including the NMDA receptor (NMDAR). NMDARs are glutamate-gated ion channels involved in excitatory synaptic transmission, synaptic plasticity, and excitotoxicity. In this study, we analyzed the effects of PS on calcium signaling in cultured hippocampal neurons and HEK293 cells expressing NMDAR. The cells were loaded with the Ca2+ sensor Fura-2. In agreement with previous electrophysiological experiments, PS potentiated the increases in intracellular Ca2+ induced by an exogenous application of glutamate; however, PS also increased intracellular Ca2+ in the absence of exogenous NMDA agonist. The agonist-independent effect of PS was induced in all neurons studied and in HEK293 cells expressing GluN1/GluN2A-B receptors in a neurosteroid-specific manner. We conclude that PS is an endogenous NMDA agonist that activates the GluN1/GluN2A-B receptors.

scholarly journals Negative Regulator of Ubiquitin-Like Protein 1 modulates the autophagy–lysosomal pathway via p62 to facilitate the extracellular release of tau following proteasome impairment

2019 ◽  
Vol 29 (1) ◽  
pp. 80-96 ◽  
Author(s):  
Rosellina Guarascio ◽  
Dervis Salih ◽  
Marina Yasvoina ◽  
Frances A Edwards ◽  
Michael E Cheetham ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Proteasome Inhibition ◽  
Ubiquitin Proteasome System ◽  
Proteasomal Degradation ◽  
Tau Phosphorylation ◽  
Negative Regulator ◽  
Autophagy Flux ◽  
Extracellular Release ◽  
Uba Domain ◽  
Ubiquitin Proteasome

Abstract Negative regulator of ubiquitin-like protein 1 (NUB1) and its longer isoform NUB1L are ubiquitin-like (UBL)/ubiquitin-associated (UBA) proteins that facilitate the targeting of proteasomal substrates, including tau, synphilin-1 and huntingtin. Previous data revealed that NUB1 also mediated a reduction in tau phosphorylation and aggregation following proteasome inhibition, suggesting a switch in NUB1 function from targeted proteasomal degradation to a role in autophagy. Here, we delineate the mechanisms of this switch and show that NUB1 interacted specifically with p62 and induced an increase in p62 levels in a manner facilitated by inhibition of the proteasome. NUB1 moreover increased autophagosomes and the recruitment of lysosomes to aggresomes following proteasome inhibition. Autophagy flux assays revealed that NUB1 affected the autophagy–lysosomal pathway primarily via the UBA domain. NUB1 localized to cytosolic inclusions with pathological forms of tau, as well as LAMP1 and p62 in the hippocampal neurons of tauopathy mice. Finally, NUB1 facilitated the extracellular release of tau following proteasome inhibition. This study thus shows that NUB1 plays a role in regulating the autophagy–lysosomal pathway when the ubiquitin proteasome system is compromised, thus contributing to the mechanisms targeting the removal of aggregation-prone proteins upon proteasomal impairment.

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