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

Nature Neuroscience volume 3, pages 311–313 (2000)Cite this article

An Erratum to this article was published on 01 May 2000

Long-term memory and long-lasting modifications of synaptic strength require active protein synthesis by participating neurons, and synaptic plasticity in vitro requires postsynaptic fusion of vesicles delivering integral membrane and/or secretory proteins. Local translation in dendrites is proposed to explain the involvement of newly synthesized proteins at selective synapses in the generation of synapse-specific plasticity. Here we report that protein translocation sites (translocons), ribosomes and lumenal ER proteins (involved in protein assembly and folding) were associated with the neuronal endomembrane system of dendrites and dendritic spines, thus allowing for the involvement of locally synthesized integral membrane and secretory proteins in synapse-specific modification.

Dendritic targeting of mRNA is reported1,2, and mRNA species encoding specific cytosolic, secretory and integral membrane proteins are found in vertebrate dendrites3,4,5. Because proteins destined for secretion or incorporation into the plasma membrane need to enter the initial portion of the secretory pathway, the rough endoplasmic reticulum (RER)6, it remains unresolved how this would occur for locally synthesized integral membrane (such as receptors) and secretory proteins in dendrites. Synthesis of such proteins would require either targeting to the perinuclear endoplasmic reticulum (ER) or local translocation into the ER of dendrites. In addition to the perinuclear RER, neurons have a contiguous endomembrane system extending into dendrites and dendritic spines; this structure is traditionally viewed as smooth endoplasmic reticulum7,8. If translocation sites, whose presence define the RER, were located in dendritic endomembranes, then local protein translation and translocation could occur at these sites, potentially subserving synapse-specific modifications. Translocon channels in the RER function as entry sites. In mammals, the main constituent of the translocon is the Sec61 protein complex9. Because the Sec61 complex alone is necessary and sufficient for interaction with ribosomes carrying nascent polypeptide chains and subsequent translocation10, we chose to investigate the ultrastructural localization of the translocon Sec61α central subunit protein. In addition, because protein translocation in mammals is thought to occur co-translationally, while the ribosome–nascent chain complex is docked at the translocon, we assessed potential active translocation sites by localizing ribosomes and lumenal ER proteins to regions of the endomembrane system that were also labeled for Sec61α. We examined the hippocampal formation, a brain region involved in explicit memory and widely analyzed in studies of synaptic plasticity11. Studies of synaptic plasticity in the hippocampal CA1 and dentate gyrus (DG) regions yield characterization of long-term potentiation (LTP), an understanding of the dependency of the long-term phases of information storage on protein synthesis11 and theories regarding the potential role of local protein synthesis in synapse specificity12.

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Figure 1: Localization of Sec61α to the endomembrane of dendritic spines and dendrites.
Figure 2: Localization of ribosomes and lumenal ER proteins within dendritic spines and dendrites.

Notes

  1. Because of an editorial error, the heading for Table 1, part b was printed incorrectly. The numbers shown are particles per 1000 μm, not particles per 1000 mm.

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Acknowledgements

We wish to thank Michael J. Caplan, Teri A. Milner, Martin Wiedmann and Jeffrey D. White for their support and assistance.

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  1. J. B. McCarthy

    Present address: Department of Neurobiology, Weill Medical College of Cornell University, Room 410, 411 East 69th Street, New York, New York, 10021, USA

Authors and Affiliations

  1. Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, 10021, New York, USA

    J. P. Pierce

  2. Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, 10021, New York, USA

    K. van Leyen

  3. Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, 06520, Connecticut , USA

    J. B. McCarthy

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  1. J. P. Pierce
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Correspondence to J. B. McCarthy.

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Pierce, J., van Leyen, K. & McCarthy, J. Translocation machinery for synthesis of integral membrane and secretory proteins in dendritic spines. Nat Neurosci 3, 311–313 (2000). https://doi.org/10.1038/73868

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