Translational Control Mechanisms in Long-lasting Synaptic Plasticity and Memory

Gkogkas, Christos G.; Sonenberg, Nahum; Costa-Mattioli, Mauro

doi:10.1074/jbc.r110.154476

Cited by 63 publications

(59 citation statements)

References 59 publications

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“…This indicates that even a mild activation of the mTORC1 signaling can bring about a drastic effect on synaptic plasticity and learning associated with various diseases (Lim and Crino, 2013), while a mild inhibition of mTORC1 appears not to affect memory functions (Goorden et al, 2015). This is in accordance with the need to use high concentrations of rapamycin for impairing learning and plasticity in mice (Gkogkas et al, 2010;Goorden et al, 2015). The relative non-responsiveness in the synaptic plasticity by reduction of Rheb may also be due to the existence of Rheb2, which also activates mTORC1 (Tee et al, 2005).…”

Section: Rheb In Synapse Size and Functionsupporting

confidence: 63%

“…An interesting finding on the role of Rheb-mTORC1 canonical pathway in memory formation of the mollusk, Aplysia californica, was from Weatherill et al, where S6 activated by Rheb act as a critical regulator of 24 h-LTF ( Weatherill et al, 2010). S6K-and 4E-BP1-mediated translation is required for synaptic plasticity and for cognitive processing in both vertebrates and invertebrates (Antion et al, 2008;Gkogkas et al, 2010;Weatherill et al, 2010).…”

Section: Rheb In Synapse Size and Functionmentioning

confidence: 99%

“…mTORC1-mediated translation is required both at the synapse, for synaptic plasticity, and within the cell soma, for maintaining memory (Swiech et al, 2008;Gkogkas et al, 2010).…”

Section: Rheb In Synapse Size and Functionmentioning

confidence: 99%

“…Rapamycin is an immunosuppressant and anticancer agent that binds to a 12-kDa FK506-binding protein (FKBP12) with high affinity. The FKBP12-rapamycin complex then acts on mTOR to inhibit mTORC1 function and thereby inhibit cell growth Loewith et al, 2002;Hay and Sonenberg, 2004;Adami et al, 2007;Gkogkas et al, 2010). mTORC2, in addition to mTOR and mLST8, contains the essential polypeptides: rapamycininsensitive companion of mTOR (rictor) and mammalian stress-activated map kinase-interacting protein 1 (mSin1) (Loewith et al, 2002;Sarbassov et al, 2004;Adami et al, 2007;Avruch and Long, 2009).…”

Section: Rheb Signaling Pathwaymentioning

confidence: 99%

“…Synaptic plasticity is measured as long-term potentiation (LTP) and long-term depression (LTD) in vertebrates and as long-term facilitation (LTF) in invertebrates (Gkogkas et al, 2010;Hoeffer and Klann, 2010). An interesting finding on the role of Rheb-mTORC1 canonical pathway in memory formation of the mollusk, Aplysia californica, was from Weatherill et al, where S6 activated by Rheb act as a critical regulator of 24 h-LTF ( Weatherill et al, 2010).…”

Section: Rheb In Synapse Size and Functionmentioning

confidence: 99%

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Rheb in neuronal degeneration, regeneration, and connectivity

Potheraveedu

Schöpel

Stoll

et al. 2017

Biological Chemistry

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Abstract:The small GTPase Rheb was originally detected as an immediate early response protein whose expression was induced by NMDA-dependent synaptic activity in the brain. Rheb's activity is highly regulated by its GTPase activating protein (GAP), the tuberous sclerosis complex protein, which stimulates the conversion from the active, GTP-loaded into the inactive, GDP-loaded conformation. Rheb has been established as an evolutionarily conserved molecular switch protein regulating cellular growth, cell volume, cell cycle, autophagy, and amino acid uptake. The subcellular localization of Rheb and its interacting proteins critically regulate its activity and function. In stem cells, constitutive activation of Rheb enhances differentiation at the expense of self-renewal partially explaining the adverse effects of deregulated Rheb in the mammalian brain. In the context of various cellular stress conditions such as oxidative stress, ER-stress, death factor signaling, and cellular aging, Rheb activation surprisingly enhances rather than prevents cellular degeneration. This review addresses cell type-and cell state-specific function(s) of Rheb and mainly focuses on neurons and their surrounding glial cells. Mechanisms will be discussed in the context of therapy that interferes with Rheb's activity using the antibiotic rapamycin or low molecular weight compounds.

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Section: Rheb In Synapse Size and Functionsupporting

confidence: 63%

Section: Rheb In Synapse Size and Functionmentioning

confidence: 99%

“…mTORC1-mediated translation is required both at the synapse, for synaptic plasticity, and within the cell soma, for maintaining memory (Swiech et al, 2008;Gkogkas et al, 2010).…”

Section: Rheb In Synapse Size and Functionmentioning

confidence: 99%

Section: Rheb Signaling Pathwaymentioning

confidence: 99%

Section: Rheb In Synapse Size and Functionmentioning

confidence: 99%

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Rheb in neuronal degeneration, regeneration, and connectivity

Potheraveedu

Schöpel

Stoll

et al. 2017

Biological Chemistry

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Calcium triggers the dissociation of myosin‐Va from ribosomes in ribonucleoprotein complexes

et al. 2020

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The sorting of RNAs to specific regions of the cell for local translation represents an important mechanism directing protein distribution and cell compartmentalization. While significant progress has been made in understanding the mechanisms underlying the transport and localization of mRNAs, the mechanisms governing ribosome mobilization are less well understood. Ribosomes present in the cytoplasm of multiple cell types can form ribonucleoprotein complexes that also contain myosin-Va (Myo5a), a processive, actin-dependent molecular motor. Here, we report that Myo5a can be disassociated from ribosomes when ribonucleoprotein complexes are exposed to calcium, both in vitro and in vivo. We suggest that Myo5a may act as a molecular switch able to anchor or release ribosomes from the actin cytoskeleton in response to intracellular signaling.

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Upregulation of eIF4E, but not other translation initiation factors, in dendritic spines during memory formation

Gindina

Botsford

Cowansage

et al. 2021

J of Comparative Neurology

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Local translation can provide a rapid, spatially targeted supply of new proteins in distal dendrites to support synaptic changes that underlie learning. Learning and memory are especially sensitive to manipulations of translational control mechanisms, particularly those that target the initiation step, and translation initiation at synapses could be a means of maintaining synapse specificity during plasticity. Initiation predominantly occurs via recruitment of ribosomes to the 5 0 mRNA cap by complexes of eukaryotic initiation factors (eIFs), and the interaction between eIF4E and eIF4G1 is a particularly important target of translational control pathways. Pharmacological inhibition of eIF4E-eIF4G1 binding impairs formation of memory for aversive Pavlovian conditioning as well as the accompanying increase in polyribosomes in the heads of dendritic spines in the lateral amygdala (LA). This is consistent with a role for initiation at synapses in memory formation, but whether eIFs are even present near synapses is unknown. To determine whether dendritic spines contain eIFs and whether eIF distribution is affected by learning, we combined immunolabeling with serial section transmission electron microscopy (ssTEM) volume reconstructions of LA dendrites after Pavlovian conditioning. Labeling for eIF4E, eIF4G1, and eIF2α-another key target of regulation-occurred in roughly half of dendritic spines, but learning effects were only found for eIF4E, which was upregulated in the heads of dendritic spines. Our results support the possibility of regulated translation initiation as a means of synapse-specific protein targeting during learning and are consistent with the model of eIF4E availability as a central point of control.

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Translational Control Mechanisms in Long-lasting Synaptic Plasticity and Memory

Cited by 63 publications

References 59 publications

Rheb in neuronal degeneration, regeneration, and connectivity

Rheb in neuronal degeneration, regeneration, and connectivity

Calcium triggers the dissociation of myosin‐Va from ribosomes in ribonucleoprotein complexes

Upregulation of eIF4E, but not other translation initiation factors, in dendritic spines during memory formation

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