Involvement of Protein Synthesis and Degradation in Long-Term Potentiation of Schaffer Collateral CA1 Synapses

Karpova, Anna; Mikhaylova, Marina; Thomas, Ulrike; Knöpfel, Thomas; Behnisch, Thomas

doi:10.1523/jneurosci.4573-05.2006

Cited by 153 publications

(119 citation statements)

References 61 publications

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“…Although the dynamics of Arc turnover remains to be directly studied, rapid turnover of Arc (on the order of minutes to hours) has been reported in several in vitro studies (Yin et al, 2002;Rao et al, 2006). Interestingly, two recent studies showed that drugs that block proteosome-dependent degradation of proteins, such as protein synthesis inhibitors, prevent formation of stable LTP (Fonseca et al, 2006;Karpova et al, 2006). This surprising observation suggested that stable LTP involves simultaneous rapid synthesis and degradation of proteins.…”

Section: Discussionmentioning

confidence: 99%

Sustained Arc/Arg3.1 Synthesis Controls Long-Term Potentiation Consolidation through Regulation of Local Actin Polymerization in the Dentate GyrusIn Vivo

Messaoudi¹,

Kanhema²,

Soulé³

et al. 2007

J. Neurosci.

416

463

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New gene expression is necessary for long-term potentiation (LTP) consolidation, yet roles for specific activity-induced mRNAs have not been defined. Here we probed the dynamic function of activity-induced Arc (activity-regulated cytoskeletal-associated protein)/Arg3.1 (activity-regulated gene 3.1 protein homolog) mRNA using brief, local infusions of antisense (AS) oligodeoxynucleotides at multiple time points during dentate gyrus LTP in vivo. Surprisingly, early Arc synthesis is necessary for early expression of LTP, whereas sustained synthesis is required to generate stably modified synapses. AS application 2 h after LTP induction results in a rapid and permanent reversal of LTP. This reversal is associated with rapid knockdown of upregulated Arc, dephosphorylation of actin depolymerization factor/cofilin, and loss of nascent filamentous actin (F-actin) at synaptic sites. Infusion of the F-actin stabilizing drug jasplakinolide during LTP maintenance blocks the ability of AS to reverse LTP. These results couple activity-induced expression of Arc to expansion of the actin cytoskeleton underlying enduring LTP. Furthermore, Arc synthesis is required for both the induction and consolidation of LTP elicited by local BDNF infusion, thus identifying Arc as a key molecular effector of BDNF in synaptic plasticity.

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Section: Discussionmentioning

confidence: 99%

Sustained Arc/Arg3.1 Synthesis Controls Long-Term Potentiation Consolidation through Regulation of Local Actin Polymerization in the Dentate GyrusIn Vivo

Messaoudi¹,

Kanhema²,

Soulé³

et al. 2007

J. Neurosci.

416

463

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“…Additional investigation into the expression patterns of the Thy1-Usp14LF transgene should provide important insights into the dysfunctional neuronal circuit or circuits in the ax J mice. It is becoming increasingly clear that changes in the activity of the UPS play an important role in both synaptic plasticity and disease (Wilson et al, 2002;Speese et al, 2003;Yi and Ehlers, 2005;Karpova et al, 2006;Patrick, 2006). It is therefore possible that Usp14 has evolved a specialized function in neurons to regulate the ubiquitin side chain length of proteins bound to the proteasome.…”

Section: Discussionmentioning

confidence: 99%

Transgenic Rescue ofataxiaMice with Neuronal-Specific Expression of Ubiquitin-Specific Protease 14

Crimmins¹,

Jin²,

Wheeler³

et al. 2006

J. Neurosci.

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The ataxia mutation (ax J ) is a recessive neurological mutation that results in reduced growth, ataxia, and hindlimb muscle wasting in mice. The ax J gene encodes ubiquitin-specific protease 14 (Usp14), a deubiquitinating enzyme (DUB) that associates with the proteasome via its ubiquitin-like (Ubl) domain and is involved in processing ubiquitin chains. Analysis of Usp14 gene products demonstrated that Usp14 undergoes alternative pre-mRNA splicing to produce a full-length form of Usp14 that is capable of binding proteasomes and a form that contains a deletion in the Ubl domain. The full-length form of Usp14 is the only form that appears to be reduced in the ax J mice. Transgenic rescue of the ax J mice with neuronal-specific expression of Usp14 demonstrated that the full-length form of Usp14 was sufficient to restore viability and motor system function to the ax J mice. Biochemical analysis showed that the ubiquitin hydrolyase activity of this form of Usp14 is dependent on the presence of proteasomes, and neuronal expression of full-length Usp14 was able to restore the levels of monomeric ubiquitin in the brains of ax J mice. However, the ax J -rescued mice still displayed the Purkinje cell axonal swellings that are seen in the ax J mice, indicating that this cerebellar alteration is not the primary cause of the ax J movement disorders. These results show that the motor defects observed in the ax J mice are attributable to a neuropathic disease rather than to a muscular disorder and suggest that changes in proteasomal function may contribute to neurological dysfunction in the ax J mice.

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“…Palmitoylation of PSD-95 favors its synaptic localization (ElHusseini Ael et al 2002). Activity-dependent degradation of synaptic proteins-which is required for LTP and LTD, as well as learning and memory (Colledge et al 2003;Fonseca et al 2006;Karpova et al 2006;Lee et al 2008)-may be aided by the rapid redistribution of proteasomes to postsynaptic sites following synaptic stimulation (Bingol and Schuman 2006;Bingol et al 2010).…”

Section: Basal and Activity-dependent Protein Turnover In The Psdmentioning

confidence: 99%

The Postsynaptic Organization of Synapses

Sheng¹,

Kim²

2011

Cold Spring Harbor Perspectives in Biology

475

426

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The postsynaptic side of the synapse is specialized to receive the neurotransmitter signal released from the presynaptic terminal and transduce it into electrical and biochemical changes in the postsynaptic cell. The cardinal functional components of the postsynaptic specialization of excitatory and inhibitory synapses are the ionotropic receptors (ligandgated channels) for glutamate and g-aminobutyric acid (GABA), respectively. These receptor channels are concentrated at the postsynaptic membrane and embedded in a dense and rich protein network comprised of anchoring and scaffolding molecules, signaling enzymes, cytoskeletal components, as well as other membrane proteins. Excitatory and inhibitory postsynaptic specializations are quite different in molecular organization. The postsynaptic density of excitatory synapses is especially complex and dynamic in composition and regulation; it contains hundreds of different proteins, many of which are required for cognitive function and implicated in psychiatric illness. E xcitatory synapses on principal neurons of mammalian brain occur mainly on tiny protrusions called dendritic spines (Bourne and Harris 2008). In contrast, inhibitory synapses are formed on the shaft of dendrites, or on cell bodies and axon initial segments. The postsynaptic side of excitatory synapses differs from inhibitory synapses not only in their content of neurotransmitter receptors but also in their morphology and molecular composition and organization. In part because of their greater abundance and distinctive structure, much more is known about the postsynaptic organization of central excitatory (glutamatergic) synapses. THE POSTSYNAPTIC DENSITY OF EXCITATORY SYNAPSESExcitatory synapses are characterized by a morphological and functional specialization of the postsynaptic membrane called the postsynaptic density (PSD), which is usually located at the tip of the dendritic spine. The PSD contains the glutamate receptors that are activated by the glutamate neurotransmitter released from the presynaptic terminal, as well as a host of associated signaling and structural molecules. A set of abundant scaffold proteins holds together the PSD by binding to the glutamate receptors, other postsynaptic receptors and adhesion

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Involvement of Protein Synthesis and Degradation in Long-Term Potentiation of Schaffer Collateral CA1 Synapses

Cited by 153 publications

References 61 publications

Sustained Arc/Arg3.1 Synthesis Controls Long-Term Potentiation Consolidation through Regulation of Local Actin Polymerization in the Dentate GyrusIn Vivo

Sustained Arc/Arg3.1 Synthesis Controls Long-Term Potentiation Consolidation through Regulation of Local Actin Polymerization in the Dentate GyrusIn Vivo

Transgenic Rescue ofataxiaMice with Neuronal-Specific Expression of Ubiquitin-Specific Protease 14

The Postsynaptic Organization of Synapses

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