A New Component in Synaptic Plasticity: Upregulation of Kinesin in the Neurons of the Gill-Withdrawal Reflex

Puthanveettil, Sathyanarayanan V.; Monje, Francisco J.; Miniaci, Maria Concetta; Choi, Yun-Beom; Karl, Kevin A.; Khandros, Eugene; Gawinowicz, Mary Ann; Sheetz, Michael P.; Kandel, Eric R.

doi:10.1016/j.cell.2008.11.003

Cited by 85 publications

(104 citation statements)

References 43 publications

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“…55 In a later study, we demonstrated that knockdown of ApKHC1 blocked the initiation of LTF; however, once the LTF is initiated, knockdown of ApKHC1 does not block persistence. 40 Knockdown experiments of ApMHC, actin-dependent molecular motor, and mRNA cargo of ApKHC1, also showed similar results on initiation and persistence of LTF. 52 Together, these studies suggest that during persistence of memory, synapses become autonomous with respect to transport from the cell body, and RNAs are stored at the synapses for later use.…”

Section: When and How Are The Synaptically Localizedmentioning

confidence: 49%

“…Indeed, several synaptic proteins required for synapse formation (e.g., neurexin, neuroligin, piccolo, and bassoon) were found in the kinesin complex isolated from the CNS, which are required for the establishment of LTF. 39,40 Next, we searched for RNAs in the ApKHC1 complexes isolated from the Aplysia CNS. Since kinesin is the major motor that mediates the microtubuledependent transport of gene products from the cell body to distal neuronal processes, we assumed that molecular characterization of the kinesin complex would identify RNAs transported to synapses.…”

Section: Is the Kinesin-mediated Transport Of Proteins And Rnas Impormentioning

confidence: 99%

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RNA transport and long-term memory storage

Puthanveettil

2013

RNA Biology

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Their observations suggested that mRNAs and the machinery for protein translation are transported to synapses. Several later studies have shown that RNAs are localized to distal parts of neurons in both vertebrates and invertebrates. Sequencing of RNAs prepared from microdissected neuronal processes of sensory neurons of Aplysia led to the identification of a few hundred RNAs that are enriched in neuronal processes.2,3 Using a microarraybased approach, RNAs localized to dendrites of hippocampal neurons were identified. 4 Recently, RNaseq analysis identified a few thousand RNAs localized to the dendritic layer of the hippocampus. 5 What Is the Significance of Transcriptome Localized to Synapses?Several studies have shown that RNAs localized to synapses are used for synthesizing new proteins, which are necessary for synaptogenesis and activitydependent synaptic remodeling. Local protein synthesis has a significant role in long-term memory storage (LTM) in the marine snail Aplysia, 6-10 the fruit fly Drosophila, 11,12 and in mice. [13][14][15][16] Localization of specific mRNAs provides an efficient regulatory mechanism for restricting gene expression to specific subcellular locations in neurons and an elegant mechanism for synapse-specific plasticity.9,17 It allows individual synapses to undergo specific changes such as remodeling and growth in response to specific stimuli, such as learning. Such modifications can occur independently of unstimulated synapses in a persistent, protein synthesis-dependent manner. In a study using bifurcated sensory neurons of the marine snail Aplysia, Martin and colleagues described the role of mRNA translation during synapse-specific longterm facilitation (LTF).9 Synapse-specific translation is also critical for long-term potentiation (LTP) in the hippocampus. 18LTF and LTP are considered the cellular analogs of learning and RNA transport and long-term memory storage

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Section: When and How Are The Synaptically Localizedmentioning

confidence: 49%

Section: Is the Kinesin-mediated Transport Of Proteins And Rnas Impormentioning

confidence: 99%

RNA transport and long-term memory storage

Puthanveettil

2013

RNA Biology

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“…1A) following a previously published protocol (13) and analyzed by silver stain and Western blot analysis (Fig. 1B).…”

Section: Isolation and Characterization Of Protein Complexes Of Molecmentioning

confidence: 99%

“…To identify actively transported proteins, we focused on the protein complexes associated with kinesins, molecular motor proteins that move from the cell body to distal neuronal processes and mediate the transport of various gene products (9,13). We considered that proteins associated with kinesins include both synaptic proteins and proteins localized to dendrites and axons.…”

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confidence: 99%

New approach to capture and characterize synaptic proteome

Liu¹,

Kadakkuzha²,

Pascal³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Little is known regarding the identity of the population of proteins that are transported and localized to synapses. Here we describe a new approach that involves the isolation and systematic proteomic characterization of molecular motor kinesins to identify the populations of proteins transported to synapses. We used this approach to identify and compare proteins transported to synapses by kinesin (Kif) complexes Kif5C and Kif3A in the mouse hippocampus and prefrontal cortex. Approximately 40-50% of the protein cargos identified in our proteomics analysis of kinesin complexes are known synaptic proteins. We also found that the identity of kinesins and where they are expressed determine what proteins they transport. Our results reveal a previously unappreciated role of kinesins in regulating the composition of synaptic proteome.kinesin | protein transport | synapse | proteome | hippocampus

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“…Because the CNS contains both neuronal and nonneuronal cells, this approach will also yield RNAs found in the kinesin complex in nonneuronal cells, such as glia. We first optimized conditions for isolating RNA transport complexes from the CNS of Aplysia based on a previously described protocol for preparation of kinesin transport complexes Aplysia Kinesin Heavy Chain 1 (ApKHC1) that contain several synaptic proteins (15). To examine whether the transport complexes prepared from CNS contain RNA cargos ( Fig.…”

Section: Strategy For Identifying Synaptically Targeted Rnas: Isolatimentioning

confidence: 99%

A strategy to capture and characterize the synaptic transcriptome

Puthanveettil

Antonov²,

Kalachikov

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Here we describe a strategy designed to identify RNAs that are actively transported to synapses during learning. Our approach is based on the characterization of RNA transport complexes carried by molecular motor kinesin. Using this strategy in Aplysia, we have identified 5,657 unique sequences consisting of both coding and noncoding RNAs from the CNS. Several of these RNAs have key roles in the maintenance of synaptic function and growth. One of these RNAs, myosin heavy chain, is critical in presynaptic sensory neurons for the establishment of long-term facilitation, but not for its persistence.long-term memory storage | RNA transport | local protein synthesis | neurogenomics | cystoskeleton D espite decades of research on the importance of local translation in learning-related synaptic plasticity and long-term memory storage, we know relatively little about the identity of the "synaptic transcriptome," the various components of the total RNA population that is transported from the cell body, and how this transcriptome becomes localized to and translated at specific synapses (1-12). To develop a general strategy for isolating and characterizing all of the RNAs transported from the cell body to the synapse, we have focused on the RNA transport complexes that interact with the molecular motor kinesin that mediate transport of gene products from the cell body to synapses (13,14).Our approach offers four distinct advantages over previously described methods: (i) it allows the identification of RNAs based on their association with transport machinery that is destined for synapses; (ii) it reflects dynamically regulated RNAs; (iii) it allows for identification of the targeted RNAs; and (iv) it can be used in different regions of the central nervous system (CNS), thereby facilitating genomic characterization of synaptic transcriptome of the entire CNS or region of the CNS. These advantages should aid the study of stoichiometric changes in localized RNAs and their role of local translation, not only in memory storage, but also in a variety of other physiological conditions, such as development. Using this strategy, we have succeeded in obtaining a comprehensive collection of RNAs targeted to Aplysia CNS synapses. We further show that myosin heavy chain mRNA, a cargo of kinesin, is localized to sensory neuron processes and is required specifically for the induction of long-term facilitation (LTF) at sensory and motor neuron synapses. Results Strategy for Identifying Synaptically Targeted RNAs: Isolation andCharacterization of RNA Transport Complexes. We assumed that successful isolation of the RNA-protein complexes associated with the kinesin transport machinery would help identify the full repertoire of RNAs that are actively transported to synapses. Because the CNS contains both neuronal and nonneuronal cells, this approach will also yield RNAs found in the kinesin complex in nonneuronal cells, such as glia. We first optimized conditions for isolating RNA transport complexes from the CNS of Aplysia based on a previous...

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A New Component in Synaptic Plasticity: Upregulation of Kinesin in the Neurons of the Gill-Withdrawal Reflex

Cited by 85 publications

References 43 publications

RNA transport and long-term memory storage

RNA transport and long-term memory storage

New approach to capture and characterize synaptic proteome

A strategy to capture and characterize the synaptic transcriptome

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