Nuclear Translocation of CAM-Associated Protein Activates Transcription for Long-Term Facilitation in Aplysia

Lee, Seung‐Hee; Lim, Chae‐Seok; Park, Hyungju; Lee, Jina; Han, Jin Hee; Kim, Hyoung; Cheang, Ye-Hwang; Lee, Sue-Hyun; Lee, Yong Seok; Ko, Hyoung‐Gon; Jang, Dong-Hyuk; Kim, Hyong-Kyu; Miniaci, Maria Concetta; Bartsch, Dušan; Kim, Eunjoon; Bailey, Craig H.; Kandel, Eric R.; Kaang, Bong‐Kiun

doi:10.1016/j.cell.2007.03.041

Cited by 49 publications

(34 citation statements)

References 29 publications

(66 reference statements)

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“…Moreover, this branch-specificity requires CREB-1 activation in the presynaptic sensory neurons. Thus, signals are sent not only from the synapse back to the nucleus (Martin and Kandel 1996;Lee et al 2007), but also from the nucleus to specific synapses. In other words, these results indicate that the molecular dialogue required for synapse-specific long-term memory is bidirectional.…”

Section: The Maintenance Of Long-term Memorymentioning

confidence: 99%

Functional Prions in the Brain

Rayman

Kandel

2016

Cold Spring Harb Perspect Biol

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Prions are proteins that can adopt self-perpetuating conformations and are traditionally regarded as etiological agents of infectious neurodegenerative diseases in humans, such as Creutzfeldt-Jakob disease, kuru, and transmissible encephalopathies. More recently, a growing consensus has emerged that prion-like, self-templating mechanisms also underlie a variety of neurodegenerative disorders, including amyotrophic lateral sclerosis, Alzheimer's disease, and Huntington's disease. Perhaps most surprising, not all prion-like aggregates are associated with pathological changes. There are now several examples of prion-like proteins in mammals that serve positive biological functions in their aggregated state. In this review, we discuss functional prions in the nervous system, with particular emphasis on the cytoplasmic polyadenylation element-binding protein (CPEB) and the role of its prion-like aggregates in synaptic plasticity and memory. We also mention a more recent example of a functional prion-like protein in the brain, TIA-1, and its role during stress. These studies of functional prion-like proteins have provided a number of generalizable insights on how prion-based protein switches may operate to serve physiological functions in higher eukaryotes.

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Section: The Maintenance Of Long-term Memorymentioning

confidence: 99%

Functional Prions in the Brain

Rayman

Kandel

2016

Cold Spring Harb Perspect Biol

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“…Stimulus-induced nuclear import of transcription factors provides a potentially more direct means of signaling from sites of stimulation to the nucleus (30,31). A number of transcription factors and transcriptional regulators, including NF B, Elk-1, NFAT, and CAMAP have indeed been shown to translocate from distal processes to the nucleus in neurons (32)(33)(34)(35)(36).…”

Section: Discussionmentioning

confidence: 99%

Importin-mediated retrograde transport of CREB2 from distal processes to the nucleus in neurons

Lai¹,

Zhao²,

Ch’ng³

et al. 2008

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

103

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Signals received at distal synapses of neurons must be conveyed to the nucleus to initiate the changes in transcription that underlie long-lasting synaptic plasticity. The presence of importin nuclear transporters and of select transcription factors at synapses raises the possibility that importins directly transport transcription factors from synapse to nucleus to modulate gene expression. Here, we show that cyclic AMP response element binding protein 2 (CREB2)/activating transcription factor 4 (ATF4), a transcriptional repressor that modulates long-term synaptic plasticity and memory, localizes to distal dendrites of rodent hippocampal neurons and neurites of Aplysia sensory neurons (SNs) and binds to specific importin ␣ isoforms. Binding of CREB2 to importin ␣ is required for its transport from distal dendrites to the soma and for its translocation into the nucleus. CREB2 accumulates in the nucleus during long-term depression (LTD) but not long-term potentiation of rodent hippocampal synapses, and during LTD but not long-term facilitation (LTF) of Aplysia sensory-motor synapses. Time-lapse microscopy of CREB2 tagged with a photoconvertible fluorescent protein further reveals retrograde transport of CREB2 from distal neurites to the nucleus of Aplysia SN during phenylalaninemethionine-arginine-phenylalanine-amide (FMRFamide)-induced LTD. Together, our findings indicate that CREB2 is a novel cargo of importin ␣ that translocates from distal synaptic sites to the nucleus after stimuli that induce LTD of neuronal synapses.Aplysia ͉ hippocampus ͉ transcription ͉ long-term depression ͉ dendra S ynaptic plasticity is critical to cognition and memory formation. Long-lasting forms of synaptic plasticity require both transcription and translation (1-3), and specific patterns and strengths of synaptic stimulation trigger changes in neuronal gene expression (4). However, relatively little is known about how signals are transported from synapse to nucleus to regulate transcription. Many types of synaptic stimulation induce depolarization and electrochemical signaling to rapidly alter transcription in the nucleus (5). A slower, more persistent mechanism of signaling to the nucleus involves the transport of soluble molecules from stimulated synapses to the nucleus (6, 7). Recent studies have indicated that this type of transport may involve the active nuclear import pathway (8-10).In the classical nuclear import pathway, proteins bearing nuclear localization signals (NLSs) bind an adaptor protein of the importin ␣ family, which in turn binds the importin ␤1 nuclear transporter. Importin ␤1 mediates facilitated translocation of this heterotrimeric complex across the nuclear pore. In neurons, importins may also function to carry signals from distal neuronal processes to the soma and into the nucleus (8-11). This finding raises a critical question: what are the synaptically localized cargoes of importins that translocate to the nucleus to alter transcription during synaptic plasticity?One attractive class of potential importin...

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“…only from the synapse back to the nucleus (Martin et al 1997a;Lee et al 2007), but also from the nucleus to specific synapses.…”

Section: A Metastable Protein Conformation Switch For Synapse-specifimentioning

confidence: 99%

The Role of Functional Prion-Like Proteins in the Persistence of Memory

Kandel

2016

Cold Spring Harb Perspect Biol

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105

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Nuclear Translocation of CAM-Associated Protein Activates Transcription for Long-Term Facilitation in Aplysia

Cited by 49 publications

References 29 publications

Functional Prions in the Brain

Functional Prions in the Brain

Importin-mediated retrograde transport of CREB2 from distal processes to the nucleus in neurons

The Role of Functional Prion-Like Proteins in the Persistence of Memory

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