The 3′-untranslated region of CaMKIIα is a cis-acting signal for the localization and translation of mRNA in dendrites

Mayford, Mark; Baranes, Danny; Podsypanina, Katrina; Kandel, Eric R.

doi:10.1073/pnas.93.23.13250

Cited by 312 publications

(239 citation statements)

References 29 publications

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“…Active protein synthesis has been demonstrated in dendrites in vitro (Torre and Steward, 1992;Crino and Eberwine, 1996) and in vivo (Mayford et al, 1996). Neurotrophin-induced synaptic plasticity in the hippocampus has been reported to depend on local protein synthesis in CA1 pyramidal cell dendrites (Kang and Schuman, 1996).…”

Section: Abstract: Neuronal Bc1 Rna; Rna Transport; Dendrites; Targementioning

confidence: 99%

RNA Transport in Dendrites: Acis-Acting Targeting Element Is Contained within Neuronal BC1 RNA

Muslimov¹,

Santi²,

et al. 1997

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In nerve cells, a select group of RNAs has been localized to dendritic domains. Here we have examined dendritic RNA transport in sympathetic neurons in primary culture, using a microinjection protocol with neuronal BC1 RNA and with BC1-derived sequence segments. After cytoplasmic microinjection, full-length BC1 RNA was selectively transported to dendrites; in contrast, control RNAs such as nuclear RNAs and randomsequence irrelevant RNAs remained restricted to cytoplasmic areas proximal to the injection sites. Chimeric RNAs were constructed that contained the full-length BC1 sequence inserted upstream or downstream of the coding regions of nondendritic mRNAs. After microinjection, such chimeric RNAs were specifically targeted to dendrites; microinjected corresponding nonchimeric mRNAs were not. Dendritic transport of BC1 RNA was rapid: the average dendritic delivery rate within the first hour after microinjection was 242 Ϯ 25 m/hr. Whereas a 5Ј-BC1 segment of 62 nucleotides was transported to dendrites to extents and at levels similar to full-length BC1 RNA, a 3Ј-BC1 segment of 60 nucleotides did not exit injected somata to any significant degree. A cis-acting dendritic targeting element is thus contained in the 5Ј part of neuronal BC1 RNA. These results demonstrate that mechanisms exist in neurons for fast and specific transport of selected RNAs to dendrites.

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Section: Abstract: Neuronal Bc1 Rna; Rna Transport; Dendrites; Targementioning

confidence: 99%

RNA Transport in Dendrites: Acis-Acting Targeting Element Is Contained within Neuronal BC1 RNA

Muslimov¹,

Santi²,

et al. 1997

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“…As an initial attempt to examine the role of G proteins and the cAMP/PKA system in sensorimotor gating, we measured PPI in wild-type and transgenic mice that express a constitutively active form of G s α (G s α*) (Abel et al, 1997a;Wand et al, 2001) and transgenic mice that express a dominant-negative form of protein kinase A, R(AB) (Abel et al, 1997b). Both transgenes are under the control of the CaMKIIα promoter that drives expression in neurons within forebrain areas including the neocortex, olfactory bulb, hippocampus, striatum, and amygdala (Mayford et al, 1996). These transgenic mice exhibited selective impairments in hippocampus-dependent forms of memory and alterations in hippocampal synaptic physiology (Abel et al, 1997a, b).…”

Section: Introductionmentioning

confidence: 99%

Sensorimotor Gating Deficits in Transgenic Mice Expressing a Constitutively Active Form of Gsα

Gould

Bizily

Tokarczyk

et al. 2003

Neuropsychopharmacol

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Schizophrenia is a complex disorder characterized by wide-ranging cognitive impairments, including deficits in learning as well as sensory gating. The causes of schizophrenia are unknown, but alterations in intracellular G-protein signaling pathways are among the molecular changes documented in patients with schizophrenia. Using the CaMKIIα promoter to drive expression in neurons within the forebrain, we have developed transgenic mice that express a constitutively active form of G s α (G s α*), the G protein that couples receptors such as the D 1 and D 5 dopamine receptors to adenylyl cyclase. We have also generated mice in which the CaMKIIα promoter drives expression of a dominant-negative form of protein kinase A, R(AB). Here, we examine startle responses and prepulse inhibition of the startle reflex (PPI) in these G s α* and R(AB) transgenic mice. G s α* transgenic mice exhibited selective deficits in PPI, without exhibiting alterations in the startle response, whereas no deficit in startle or PPI was found in the R(AB) transgenic mice. Thus, overstimulation of the cAMP/PKA pathway disrupts PPI, but the cAMP/ PKA pathway may not be essential for sensorimotor gating. G s α* transgenic mice may provide an animal model of certain endophenotypes of schizophrenia, because of the similarities between them and patients with schizophrenia in G-protein function, hippocampus-dependent learning, and sensorimotor gating.

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“…The dendritic trafficking of this transcript and the role of local translated CaMKIIa in synaptic plasticity events has been widely studied (Mayford et al, 1996;Miller et al, 2002;Ouyang et al, 1999). Other relatively abundant mRNAs in the neuropil region included the transcripts encoding for Shank1, PSD95 (postsynaptic density protein 95), Dendrin and MAP (microtubule-associated protein) 1A (Cajigas et al, 2012), all of them previously reported as dendritic mRNAs (Bockers et al, 2004;Herb et al, 1997;Muddashetty et al, 2007;Tucker et al, 1989).…”

Section: Cis-acting Elements and Mrna Transport Into Dendritesmentioning

confidence: 99%

BDNF-induced local protein synthesis and synaptic plasticity

2014

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a b s t r a c tBrain-derived neurotrophic factor (BDNF) is an important regulator of synaptic transmission and longterm potentiation (LTP) in the hippocampus and in other brain regions, playing a role in the formation of certain forms of memory. The effects of BDNF in LTP are mediated by TrkB (tropomyosin-related kinase B) receptors, which are known to be coupled to the activation of the Ras/ERK, phosphatidylinositol 3-kinase/Akt and phospholipase C-g (PLC-g) pathways. The role of BDNF in LTP is best studied in the hippocampus, where the neurotrophin acts at pre-and post-synaptic levels. Recent studies have shown that BDNF regulates the transport of mRNAs along dendrites and their translation at the synapse, by modulating the initiation and elongation phases of protein synthesis, and by acting on specific miRNAs. Furthermore, the effect of BDNF on transcription regulation may further contribute to long-term changes in the synaptic proteome. In this review we discuss the recent progress in understanding the mechanisms contributing to the short-and long-term regulation of the synaptic proteome by BDNF, and the role in synaptic plasticity, which is likely to influence learning and memory formation.This article is part of the Special Issue entitled 'BDNF Regulation of Synaptic Structure, Function, and Plasticity'.

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The 3′-untranslated region of CaMKIIα is a cis-acting signal for the localization and translation of mRNA in dendrites

Cited by 312 publications

References 29 publications

RNA Transport in Dendrites: Acis-Acting Targeting Element Is Contained within Neuronal BC1 RNA

RNA Transport in Dendrites: Acis-Acting Targeting Element Is Contained within Neuronal BC1 RNA

Sensorimotor Gating Deficits in Transgenic Mice Expressing a Constitutively Active Form of Gsα

BDNF-induced local protein synthesis and synaptic plasticity

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