Translocation machinery for synthesis of integral membrane and secretory proteins in dendritic spines

Pierce, Joseph P.; Leyen, Klaus van; McCarthy, J. Brian

doi:10.1038/73868

Cited by 85 publications

(75 citation statements)

References 15 publications

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“…Consistent with this hypothesis, various mRNAs and polyribosomes are present in these areas (9,38). Recent studies have also demonstrated the existence of endoplasmic reticulum and Golgi apparatus in the postsynaptic site opposing synaptic boutons, suggesting the presence of translational and posttranslational modification machinery in the postsynaptic regions (39,40). We showed here in cultured hippocampal neurons that eIF-4E, 4E-BP1, 4E-BP2, and mTOR are also present in the postsynaptic region.…”

Section: Discussionsupporting

confidence: 72%

A rapamycin-sensitive signaling pathway contributes to long-term synaptic plasticity in the hippocampus

Tang

Reis

Kang

et al. 2001

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

661

538

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Many forms of long-lasting behavioral and synaptic plasticity require the synthesis of new proteins. For example, long-term potentiation (LTP) that endures for more than an hour requires both transcription and translation. The signal-transduction mechanisms that couple synaptic events to protein translational machinery during long-lasting synaptic plasticity, however, are not well understood. One signaling pathway that is stimulated by growth factors and results in the translation of specific mRNAs includes the rapamycin-sensitive kinase mammalian target of rapamycin (mTOR, also known as FRAP and RAFT-1). Several components of this translational signaling pathway, including mTOR, eukaryotic initiation factor-4E-binding proteins 1 and 2, and eukaryotic initiation factor-4E, are present in the rat hippocampus as shown by Western blot analysis, and these proteins are detected in the cell bodies and dendrites in the hippocampal slices by immunostaining studies. In cultured hippocampal neurons, these proteins are present in dendrites and are often found near the presynaptic protein, synapsin I. At synaptic sites, their distribution completely overlaps with a postsynaptic protein, PSD-95. These observations suggest the postsynaptic localization of these proteins. Disruption of mTOR signaling by rapamycin results in a reduction of late-phase LTP expression induced by high-frequency stimulation; the early phase of LTP is unaffected. Rapamycin also blocks the synaptic potentiation induced by brain-derived neurotrophic factor in hippocampal slices. These results demonstrate an essential role for rapamycin-sensitive signaling in the expression of two forms of synaptic plasticity that require new protein synthesis. The localization of this translational signaling pathway at postsynaptic sites may provide a mechanism that controls local protein synthesis at potentiated synapses.

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Section: Discussionsupporting

confidence: 72%

A rapamycin-sensitive signaling pathway contributes to long-term synaptic plasticity in the hippocampus

Tang

Reis

Kang

et al. 2001

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

661

538

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“…It is important to point out that, although essential components for translocation have been detected in distal dendritic branches here (supplemental Fig. 3, available at www.jneurosci.org) and previously (Pierce et al, 2000), our finding that cargo leaves the ER does not require that all proteins exiting the ER in dendrites entered the ER in these branches. The smooth extended tubular domains of the smooth ER, which participate in vesicle-mediated export of cargo, form a continuous reticulum in dendrites (Martone et al, 1993;Krijnse-Locker et al, 1995;Cooney et al, 2002).…”

Section: Discussionmentioning

confidence: 86%

“…Previous studies have localized components of the translocon machinery to dendritic arbors (Tiedge and Brosius, 1996;Pierce et al, 2000Pierce et al, , 2001. To corroborate our in vitro findings, we compared the localization of endogenous Sar1 and Sec13 to that of the RER translocon (Sec61␣) machinery in primary neurons, thus comparing protein entry points into the ER (Sec61␣) with sites of exit (Sar1 and Sec13).…”

Section: Copii Is Assembled On Export Sites In Distal Dendritic Brancmentioning

confidence: 86%

“…In support of the existence of a dendritic secretory pathway, translation and translocon machinery components have been detected in dendritic shafts and spines as far as dendritic branch points in several neuronal types (Steward and Banker, 1992;Krijnse-Locker et al, 1995;Tiedge and Brosius, 1996;Gardiol et al, 1999;Pierce et al, 2000;Ma and Morris, 2002). There is also immunocytochemical evidence that components of a functional ER and ER-to-Golgi transport system are present in the dendrites of some cell types (De Camilli et al, 1986;Takei et al, 1992;Steward, 1992, 1996;Villa et al, 1992;Lowenstein et al, 1994;Krijnse-Locker et al, 1995;Gardiol et al, 1999;Pierce et al, 2000Pierce et al, , 2001Ma and Morris, 2002;Horton and Ehlers, 2003).…”

Section: Introductionmentioning

confidence: 83%

“…There is also immunocytochemical evidence that components of a functional ER and ER-to-Golgi transport system are present in the dendrites of some cell types (De Camilli et al, 1986;Takei et al, 1992;Steward, 1992, 1996;Villa et al, 1992;Lowenstein et al, 1994;Krijnse-Locker et al, 1995;Gardiol et al, 1999;Pierce et al, 2000Pierce et al, , 2001Ma and Morris, 2002;Horton and Ehlers, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Endoplasmic Reticulum Export Site Formation and Function in Dendrites

Aridor

Guzik²,

Bielli³

et al. 2004

J. Neurosci.

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The elongated and polarized characteristics of neurons render targeting of receptors to the plasma membrane of distal axonal projections and dendritic branches a major sorting task. Although the majority of biosynthetic cargo synthesis, transport, and sorting are believed to occur in the soma, local membrane protein translation and sorting has been reported recently to take place in dendrites and axons. We investigated where endoplasmic reticulum (ER) export occurs in dendrites using an in vitro permeabilized neuron system that enables us to specifically control the assembly of ER export sites. We show that ER export sites are assembled regularly throughout the entire dendritic tree by the regulated sequential recruitment of Sar1 and COPII (coat protein complex II). Moreover, activation of metabotropic glutamate receptors leads to the recruitment of the NMDA receptor subunit NR1 to remodeled ER export sites. We propose that regulation of receptor assembly and export from the ER in dendrites plays an important role in modulating receptor surface expression and neuronal function.

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