Protein synthesis in the dendrite

Tang, Shuang; Schuman, Erin M.

doi:10.1098/rstb.2001.0887

Cited by 61 publications

(46 citation statements)

References 93 publications

(119 reference statements)

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“…Among the NR2 subunits, the NR2A and NR2B subtypes are the most prevalent in the cerebral cortex (Watanabe et al, 1992), and of the two, the NR2B subunits are shown to be particularly influential in learning and memory (Tang et al, 1999;Tang and Schuman, 2002) as they prolong NMDA receptor currents, thus allowing greater Ca influx (Mori and Mishina, 1995;Dingledine et al, 1999). Further, Roche et al (2001) have shown that the C-terminus of NR2B subunit is sufficient for rapid internalization of the NMDA receptor.…”

Section: Author Manuscriptmentioning

confidence: 99%

In vivo blockade of N-methyl-d-aspartate receptors induces rapid trafficking of NR2B subunits away from synapses and out of spines and terminals in adult cortex

Fujisawa

Aoki

2003

Neuroscience

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We investigated the role of in vivo synaptic activity upon trafficking of the N-methyl-D-aspartate (NMDA) receptor subunit, NR2B, at mature synapses by electron microscopic immunocytochemistry. In vivo blockade of NMDA receptors was achieved by applying the NMDA receptor antagonist, D-2-amino-5-phosphonovalerate (D-APV), onto the cortical surface of one hemisphere of anesthetized adult rats. Inactive L-2-amino-5-phosphonovalerate (L-APV) was applied to the contralateral hemisphere for within-animal control and to assess basal level of NR2B subunits at synapses. Within 30 min of D-APV treatment, we observed a decrease in the number of layer I axospinous asymmetric synapses that are positively immuno-labeled for the NR2B subunits. This decrease was paralleled by reductions in the absolute number of immuno-gold particles found at these synapses. The decrease of NR2B labeling was detectable in all five animals examined. Significant reductions were seen not only at post-synaptic densities, but also within the cytoplasm of spines and axon terminals. The data demonstrate that blockade of NMDA receptors induces trafficking of NR2B subunits out of synaptic membranes, spines, and terminals. This is in sharp contrast to a previous observation that NR2A subunits move into spines and axon terminals following in vivo blockade with D-APV. These findings point to yet unknown, NMDA receptor activitydependent mechanisms that separately regulate the localization of NR2A and NR2B subunits at synapses. Keywordsactivity-dependent; D-APV; electron microscopy; immunocytochemistry; ultrastructure; postembedding colloidal gold labelingThe N-methyl-D-aspartate (NMDA) subtype of glutamate receptor plays an important role in experience-dependent plasticity. Calcium influx through this receptor can trigger a variety of downstream biochemical reactions, contributing to plasticity (Mori and Mishina, 1995;Kind and Neumann, 2001) and excitotoxicity (Lynch and Guttmann, 2002). One of many consequences of NMDA receptor activation is altered trafficking of proteins to and from the activated synapses. For example, long-term potentiation, in which the electrophysiological response to an input is augmented, is in part produced by NMDA receptor-dependent upregulation of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (see NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2010 May 24. Malenka and Nicoll, 1999). In vitro and fewer in vivo preparations have been used to demonstrate that NMDA receptors, too, are removed from or inserted into synaptic membrane (Rao and Craig, 1997;Liao et al., 1999;Quinlan et al., 1999;Heynen et al., 2000;Barria and Malinow, 2002;Grosshans et al., 2002;Tovar and Westbrook, 2002). However, since nearly all of these studies have used neonatal tissues, whether or not such dynamic properties of NMDA receptor subunits persist at mature synapses, in vivo, is a topic that remains relatively unexplored.Among the NMDA receptor subunits, the NR1 is necessary for NMD...

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Section: Author Manuscriptmentioning

confidence: 99%

In vivo blockade of N-methyl-d-aspartate receptors induces rapid trafficking of NR2B subunits away from synapses and out of spines and terminals in adult cortex

Fujisawa

Aoki

2003

Neuroscience

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“…Stimulation of synapses results in locally increased protein synthesis, which requires cytoplasmic polyadenylation and CPEB (Si et al 2003a). This local translation is required for the late phase of LTP, an electrophysiological, cellular correlate of memory (Nguyen et al 1994;Frey et al 1988;Liu and Schwartz 2003; for reviews, see Wells et al 2000;Richter 2001;Tang and Schuman 2002). Four isoforms of CPEB are found in the hippocampus (Wu et al 1998;Theis et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Vertebrate GLD2 poly(A) polymerases in the germline and the brain

Rouhana¹,

Wang²,

Buter³

et al. 2005

RNA

110

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Cytoplasmic polyadenylation is important in the control of mRNA stability and translation, and for early animal development and synaptic plasticity. Here, we focus on vertebrate poly(A) polymerases that are members of the recently described GLD2 family. We identify and characterize two closely related GLD2 proteins in Xenopus oocytes, and show that they possess PAP activity in vivo and in vitro and that they bind known polyadenylation factors and mRNAs known to receive poly(A) during development. We propose that at least two distinct polyadenylation complexes exist in Xenopus oocytes, one of which contains GLD2; the other, maskin and Pumilio. GLD2 protein interacts with the polyadenylation factor, CPEB, in a conserved manner. mRNAs that encode GLD2 in mammals are expressed in many tissues. In the brain, mouse, and human GLD2 mRNAs are abundant in anatomical regions necessary for long-term cognitive and emotional learning. In the hippocampus, mouse GLD2 mRNA colocalizes with CPEB1 and Pumilio1 mRNAs, both of which are likely involved in synaptic plasticity. We suggest that mammalian GLD2 poly(A) polymerases are important in synaptic translation, and in polyadenylation throughout the soma.

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“…The presence of the molecular machinery necessary for translation activity in spines and dendritic shafts (Steward and Levy, 1982;Tang and Schuman, 2002;Asaki et al, 2003), and the observed translocation of polyribosomes from dendritic shafts to spines following tetanic stimulation, which also increases the number of spines that contain polyribosomes (Ostroff et al, 2002), suggest that local protein synthesis may play an important role in synaptic plasticity. Accordingly, an overall increase in protein synthesis was observed in experiments where patterned synaptic stimulation was paired with muscarinic receptor activation with carbachol, in hippocampal slices (Feig and Lipton, 1993).…”

Section: Role Of Ampars In Ltpmentioning

confidence: 99%

“…The presence in dendrites of the machinery necessary for protein synthesis, together with the mRNA for AMPAR subunits, suggests that local synthesis of AMPAR subunits regulates local receptor abundance and composition (Steward and Levy, 1982;Kacharmina et al, 2000;Tang and Schuman, 2002;Asaki et al, 2003;Ju et al, 2004;Grooms et al, 2006). Accordingly, chronic activity blockade increases the synthesis of GluR1 in dendrites, and acute activation of group I metabotropic glutamate receptors (mGluRs) or acute depolarization with KCl increases the synthesis of both GluR1 and GluR2 (Ju et al, 2004).…”

Section: Expression Of Amparsmentioning

confidence: 99%