Ubiquitin ligase TRIM3 controls hippocampal plasticity and learning by regulating synaptic γ-actin levels
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Ubiquitin ligase TRIM3 controls hippocampal plasticity and learning by regulating synaptic γ-actin levels. / Schreiber, Joerg; Végh, Marlene J; Dawitz, Julia; Kroon, Tim; Loos, Maarten; Labonté, Dorthe; Li, Ka Wan; Van Nierop, Pim; Van Diepen, Michiel T; De Zeeuw, Chris I; Kneussel, Matthias; Meredith, Rhiannon M; Smit, August B; Van Kesteren, Ronald E.
In: J CELL BIOL, Vol. 211, No. 3, 09.11.2015, p. 569-86.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Ubiquitin ligase TRIM3 controls hippocampal plasticity and learning by regulating synaptic γ-actin levels
AU - Schreiber, Joerg
AU - Végh, Marlene J
AU - Dawitz, Julia
AU - Kroon, Tim
AU - Loos, Maarten
AU - Labonté, Dorthe
AU - Li, Ka Wan
AU - Van Nierop, Pim
AU - Van Diepen, Michiel T
AU - De Zeeuw, Chris I
AU - Kneussel, Matthias
AU - Meredith, Rhiannon M
AU - Smit, August B
AU - Van Kesteren, Ronald E
N1 - © 2015 Schreiber et al.
PY - 2015/11/9
Y1 - 2015/11/9
N2 - Synaptic plasticity requires remodeling of the actin cytoskeleton. Although two actin isoforms, β- and γ-actin, are expressed in dendritic spines, the specific contribution of γ-actin in the expression of synaptic plasticity is unknown. We show that synaptic γ-actin levels are regulated by the E3 ubiquitin ligase TRIM3. TRIM3 protein and Actg1 transcript are colocalized in messenger ribonucleoprotein granules responsible for the dendritic targeting of messenger RNAs. TRIM3 polyubiquitylates γ-actin, most likely cotranslationally at synaptic sites. Trim3(-/-) mice consequently have increased levels of γ-actin at hippocampal synapses, resulting in higher spine densities, increased long-term potentiation, and enhanced short-term contextual fear memory consolidation. Interestingly, hippocampal deletion of Actg1 caused an increase in long-term fear memory. Collectively, our findings suggest that temporal control of γ-actin levels by TRIM3 is required to regulate the timing of hippocampal plasticity. We propose a model in which TRIM3 regulates synaptic γ-actin turnover and actin filament stability and thus forms a transient inhibitory constraint on the expression of hippocampal synaptic plasticity.
AB - Synaptic plasticity requires remodeling of the actin cytoskeleton. Although two actin isoforms, β- and γ-actin, are expressed in dendritic spines, the specific contribution of γ-actin in the expression of synaptic plasticity is unknown. We show that synaptic γ-actin levels are regulated by the E3 ubiquitin ligase TRIM3. TRIM3 protein and Actg1 transcript are colocalized in messenger ribonucleoprotein granules responsible for the dendritic targeting of messenger RNAs. TRIM3 polyubiquitylates γ-actin, most likely cotranslationally at synaptic sites. Trim3(-/-) mice consequently have increased levels of γ-actin at hippocampal synapses, resulting in higher spine densities, increased long-term potentiation, and enhanced short-term contextual fear memory consolidation. Interestingly, hippocampal deletion of Actg1 caused an increase in long-term fear memory. Collectively, our findings suggest that temporal control of γ-actin levels by TRIM3 is required to regulate the timing of hippocampal plasticity. We propose a model in which TRIM3 regulates synaptic γ-actin turnover and actin filament stability and thus forms a transient inhibitory constraint on the expression of hippocampal synaptic plasticity.
U2 - 10.1083/jcb.201506048
DO - 10.1083/jcb.201506048
M3 - SCORING: Journal article
C2 - 26527743
VL - 211
SP - 569
EP - 586
JO - J CELL BIOL
JF - J CELL BIOL
SN - 0021-9525
IS - 3
ER -
