The role of 19S proteasome associated deubiquitinases in activity-dependent hippocampal synaptic plasticity

Di Yun; Yinghan Zhuang; Michael R Kreutz; Thomas Behnisch

doi:10.1016/j.neuropharm.2018.01.043

The role of 19S proteasome associated deubiquitinases in activity-dependent hippocampal synaptic plasticity

Standard

The role of 19S proteasome associated deubiquitinases in activity-dependent hippocampal synaptic plasticity. / Yun, Di; Zhuang, Yinghan; Kreutz, Michael R; Behnisch, Thomas.

In: NEUROPHARMACOLOGY, Vol. 133, 01.05.2018, p. 354-365.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Yun, D, Zhuang, Y, Kreutz, MR & Behnisch, T 2018, 'The role of 19S proteasome associated deubiquitinases in activity-dependent hippocampal synaptic plasticity', NEUROPHARMACOLOGY, vol. 133, pp. 354-365. https://doi.org/10.1016/j.neuropharm.2018.01.043

APA

Yun, D., Zhuang, Y., Kreutz, M. R., & Behnisch, T. (2018). The role of 19S proteasome associated deubiquitinases in activity-dependent hippocampal synaptic plasticity. NEUROPHARMACOLOGY, 133, 354-365. https://doi.org/10.1016/j.neuropharm.2018.01.043

Vancouver

Yun D, Zhuang Y, Kreutz MR, Behnisch T. The role of 19S proteasome associated deubiquitinases in activity-dependent hippocampal synaptic plasticity. NEUROPHARMACOLOGY. 2018 May 1;133:354-365. https://doi.org/10.1016/j.neuropharm.2018.01.043

Bibtex

@article{7797fe7377ac4dd7b3fedeb44411193f,

title = "The role of 19S proteasome associated deubiquitinases in activity-dependent hippocampal synaptic plasticity",

abstract = "Posttranslational modification and degradation of proteins by the ubiquitin-proteasome system (UPS) is crucial to synaptic transmission. It is well established that 19S proteasome associated deubiquitinases (DUBs) reverse the process of ubiquitination by removing ubiquitin from their substrates. However, their potential contribution to hippocampal synaptic plasticity has not been addressed in detail. Here, we report that inhibition of the 19S proteasome associated DUBs, ubiquitin C-terminal hydrolase 5 (UCHL5) and ubiquitin-specific peptidase 14 (USP14) by b-AP15 results in an accumulation of polyubiquitinated proteins and a reduction of monomeric ubiquitin without overt effects on 26S proteasome activity. b-AP15 led to a suppression of mTOR-p70S6K signaling and an increase in levels of p-p38 MAPK, two pathways essentially involved in establishing various forms of activity-dependent plasticity. Additionally, b-AP15 impaired the induction of late-phase long-term potentiation (L-LTP), induced the transformation of mGluR-mediated protein synthesis-independent long-term depression (early-LTD) to L-LTD and promoted heterosynaptic stabilization through synaptic tagging/capture (STC) in the hippocampal CA1 region of mice. The activity of 19S proteasome associated DUBs was also required for the enhancement of short-term potentiation (STP) induced by brain-derived neurotrophic factor (BDNF). Altogether, these results indicate an essential role of 19S proteasome associated DUBs in regulating activity-dependent hippocampal synaptic plasticity.",

keywords = "Animals, Brain-Derived Neurotrophic Factor, Cell Line, Transformed, Deubiquitinating Enzymes, Electric Stimulation, Excitatory Postsynaptic Potentials, Hippocampus, In Vitro Techniques, Male, Mice, Mice, Inbred C57BL, Neuronal Plasticity, Patch-Clamp Techniques, Piperidones, Protease Inhibitors, Proteasome Endopeptidase Complex, Transfection, Ubiquitin, Ubiquitination, Journal Article, Research Support, Non-U.S. Gov't",

author = "Di Yun and Yinghan Zhuang and Kreutz, {Michael R} and Thomas Behnisch",

year = "2018",

month = may,

day = "1",

doi = "10.1016/j.neuropharm.2018.01.043",

language = "English",

volume = "133",

pages = "354--365",

journal = "NEUROPHARMACOLOGY",

issn = "0028-3908",

publisher = "Elsevier Limited",

}

RIS

TY - JOUR

T1 - The role of 19S proteasome associated deubiquitinases in activity-dependent hippocampal synaptic plasticity

AU - Yun, Di

AU - Zhuang, Yinghan

AU - Kreutz, Michael R

AU - Behnisch, Thomas

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Posttranslational modification and degradation of proteins by the ubiquitin-proteasome system (UPS) is crucial to synaptic transmission. It is well established that 19S proteasome associated deubiquitinases (DUBs) reverse the process of ubiquitination by removing ubiquitin from their substrates. However, their potential contribution to hippocampal synaptic plasticity has not been addressed in detail. Here, we report that inhibition of the 19S proteasome associated DUBs, ubiquitin C-terminal hydrolase 5 (UCHL5) and ubiquitin-specific peptidase 14 (USP14) by b-AP15 results in an accumulation of polyubiquitinated proteins and a reduction of monomeric ubiquitin without overt effects on 26S proteasome activity. b-AP15 led to a suppression of mTOR-p70S6K signaling and an increase in levels of p-p38 MAPK, two pathways essentially involved in establishing various forms of activity-dependent plasticity. Additionally, b-AP15 impaired the induction of late-phase long-term potentiation (L-LTP), induced the transformation of mGluR-mediated protein synthesis-independent long-term depression (early-LTD) to L-LTD and promoted heterosynaptic stabilization through synaptic tagging/capture (STC) in the hippocampal CA1 region of mice. The activity of 19S proteasome associated DUBs was also required for the enhancement of short-term potentiation (STP) induced by brain-derived neurotrophic factor (BDNF). Altogether, these results indicate an essential role of 19S proteasome associated DUBs in regulating activity-dependent hippocampal synaptic plasticity.

AB - Posttranslational modification and degradation of proteins by the ubiquitin-proteasome system (UPS) is crucial to synaptic transmission. It is well established that 19S proteasome associated deubiquitinases (DUBs) reverse the process of ubiquitination by removing ubiquitin from their substrates. However, their potential contribution to hippocampal synaptic plasticity has not been addressed in detail. Here, we report that inhibition of the 19S proteasome associated DUBs, ubiquitin C-terminal hydrolase 5 (UCHL5) and ubiquitin-specific peptidase 14 (USP14) by b-AP15 results in an accumulation of polyubiquitinated proteins and a reduction of monomeric ubiquitin without overt effects on 26S proteasome activity. b-AP15 led to a suppression of mTOR-p70S6K signaling and an increase in levels of p-p38 MAPK, two pathways essentially involved in establishing various forms of activity-dependent plasticity. Additionally, b-AP15 impaired the induction of late-phase long-term potentiation (L-LTP), induced the transformation of mGluR-mediated protein synthesis-independent long-term depression (early-LTD) to L-LTD and promoted heterosynaptic stabilization through synaptic tagging/capture (STC) in the hippocampal CA1 region of mice. The activity of 19S proteasome associated DUBs was also required for the enhancement of short-term potentiation (STP) induced by brain-derived neurotrophic factor (BDNF). Altogether, these results indicate an essential role of 19S proteasome associated DUBs in regulating activity-dependent hippocampal synaptic plasticity.

KW - Animals

KW - Brain-Derived Neurotrophic Factor

KW - Cell Line, Transformed

KW - Deubiquitinating Enzymes

KW - Electric Stimulation

KW - Excitatory Postsynaptic Potentials

KW - Hippocampus

KW - In Vitro Techniques

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Neuronal Plasticity

KW - Patch-Clamp Techniques

KW - Piperidones

KW - Protease Inhibitors

KW - Proteasome Endopeptidase Complex

KW - Transfection

KW - Ubiquitin

KW - Ubiquitination

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.neuropharm.2018.01.043

DO - 10.1016/j.neuropharm.2018.01.043

M3 - SCORING: Journal article

C2 - 29407217

VL - 133

SP - 354

EP - 365

JO - NEUROPHARMACOLOGY

JF - NEUROPHARMACOLOGY

SN - 0028-3908

ER -