Abstract
Recent studies have shown that protein synthetic machinery consisting of polyribosomes and associated membranous cisterns is selectively localized beneath synaptic sites on neurons. In the present paper, the role of this machinery in neuronal function will be considered. We will:
-
1.
Summarize the studies that characterize the polyribosomes and define their associations with membranous cisterns. Taken together, these observations suggest the existence of a system for the synthesis and posttranslational processing of proteins at individual synaptic sites;
-
2.
Review the evidence that the protein synthetic machinery is particularly prominent during the initial formation of synaptic contacts (during early development), and during lesion-induced synaptogenesis in mature animals. These observations have led to the hypothesis that the polyribosomes produce proteins that play a role in the formation of the synaptic junction;
-
3.
Review evidence that supports the hypothesis that there is a local synthesis of protein within dendrites, as well as local glycosylation;
-
4.
Describe the evidence suggesting that at least some of the protein constituents of the synaptic junction itself are synthesized locally; and
-
5.
Descibe our studies that reveal a mechanism for selective dendritic transport of RNA; this transport mechanism permits the delivery of RNA to postsynaptic sites throughout the dendritic arbor.
We will advance the hypothesis that neurons position protein synthetic machinery together with the mRNA’s that are appropriate for particular synapses beneath synaptic contact regions. At the synaptic site, this machinery could then direct the synthesis of particular proteins that are critical for synapse formation or maintenance. The positioning of protein synthetic machinery at postsynaptic sites permits a rapid local regulation of the production of key proteins by events at individual synapses.
Author to whom all correspondence and reprint requests should be addressed.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Andersen, P., Sundberg, S. H., Sveen, O., and Wigstrom, H. (1977) Specific long-lasting potentiation of synaptic transmission in hippocampal slices. Nature 266, 736–737.
Appel. S. H. (1967) Turnover of brain messenger RNA. Nature, 213, 1253–1254.
Autilio, L. A., Appel, S. H., Pettis, P., and Gambetti, P. L. (1968) Biochemical studies of synapses in vitro. I. Protein synthesis. Biochemistry 7, 2615–2622.
Bartlett, W. P. and Banker, G. A. (1984a) An electron microscopic study of the development of axons and dendrites by hippocampal neurons in culture: I. Cells which develop without intercellular contacts. J. Neurosci. 4, 1944–1953.
Bartlett, W. P. and Banker, G. A. (1984b) An electron microscopic study of the development of axons and dendrites by hippocampal neurons in culture: II. Synaptic relationships. J. Neurosci. 4, 1944–1953.
Bliss, T. V. P. and Lomo, T. (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the anesthetized rabbit following stimulation of the perforant path. J. Physiol. 232, 331–356.
Bodian, D. (1965) A suggestive relationship of nerve cell RNA with specific synaptic sites. Proc. Natl. Acad. Sci. 53, 418–425.
Caceres, A. O., Banker, G. A., and Binder, L. (1986) Immunocytochemical localization of tubulin and microtubule-associated protein 2 during the development of hippocampal neurons in culture. J. Neurosci. 6, 714–722.
Colman, D., Kreibich, G., Frey, A. B., and Sabatini, D. (1982) Synthesis and incorporation of myelin polypeptides into CNS myelin. J. Cell Biol. 95, 598–608.
Colman, A. and Robinson, C. (1986) Protein import in organdies: Hierarchical targeting signals. Cell 46, 321–322.
Cotman, C. W. and Taylor, D. (1972a) Isolation and ultrastructural studies on synaptic complexes from rat brain. J. Cell Biol. 55, 696–711.
Cotman, C. W. and Taylor, D. (1972) Autoradio-graphic analysis of protein synthesis in synaptosomal fractions. Brain Res. 29, 366–372.
Cupello, A. and Hyden, H. (1975) Fractionation of RNA from brain synaptosomes and cytoplasmic subcellular fractions. J. Neurochem. 25, 399–406.
Davis, L., Banker, G. A., and Steward, O. (1987a) Selective dendritic transport of RNA by hippocampal neurons in culture. Nature 330, 477–479.
Davis, L., Dotti, C., Banker, G., and Steward, O. (1987b) Dendritic transport of RNA: An energy-dependent process. Neurosci. Abs. 13, 121.
Deadwyler, S. A., Dunwiddie, T., and Lynch, G. (1987) A critical level of protein synthesis is required for long-term potentiation. Synapse 1, 90–95.
DeCamilli, P., Moretti, M., Donini, S. D., Walter, U., and Lohmann, S. M. (1986) Heterogeneous distribution of the cAMP receptor protein Rll in the nervous system: Evidence for its intracellular accumulation on microtubules, microtubule-organizing center, and in the area of the Golgi complex. J. Cell Biol. 103, 189–203.
DeLarco, J., Nakagawa, S., Abramowitz, A., Bromwell, K., and Guroff, G. (1975) Polyadenylic acid-containing RNA from rat brain synaptosomes. J. Neurochem. 25, 131–137.
Desmond, N. L. and Levy, W. B. (1983) Synaptic correlates of associative potentiation/depression: An ultrastructural study in the hippocampus. Brain Res. 265, 21–30.
Desmond, N. L. and Levy, W. B. (1988) Anatomy of associative long-term synaptic modification. Long-term Potentiation: From Biophysics to Behavior(Lanfield, P. W. and Deadwyler, S. A., eds.), Liss, NY, pp. 265–305.
Dingwall, C. and Laskey, R. (1986) Protein import into the cell nucleus. Ann. Rev. Cell Biol. 2, 367–390.
Duffy, C., Teyler, T. J., and Shashoua, E. (1981) Longterm potentiation in the hippocampal slice: Evidence for stimulated secretion of newly synthesized proteins. Science 212, 1148–1151.
Fass, B. and Steward, O. (1983) Increases in protein precursor incorporation in the denervated neuropil of the dentate gyrus during reinnervation. Neurosci. 9, 633–664.
Fifkova, E., Anderson, C. A., Young, S. J., and Van Harreveld, A. (1982) Effect of anisomycin on stimulation-induced changes in dendritic spines of the dentate granule cells. J. Neurocytol. 11, 183–210.
Fifkova, E. and Van Harreveld, A. (1977) Long-lasting morphological changes in dendritic spines of dentate granule cells following sitmulation of entorhinal area. J. Neurocytol. 6, 211–230.
Freund, T. F., Martin, K. A. C., Smith, A. D., and Somogyi, P. (1983) Glutamate decarboxylaseimmunoreactive terminals of Golgi-impregnated axoaxonic cells and of presumed basket cells in synaptic contact with pyramidal neurons of the cat’s visual cortex. J. Comp. Neurol. 221, 263–278.
Gambetti, P., Autilio-Gambetti, L. A., Gonatas, N. K., and Shafer, B. (1972) Protein synthesis in synaptosomal fractions: Ultrastructural radioautographic study. J. Cell. Biol. 52, 526–535.
Greenough, W. T., Hwang, H.-M. F., and Gorman, C. (1985) Evidence.for active synapse formation or altered postsynaptic metabolism in visual cortex of rats reared in complex environments. Proc. Natl. Acad. Sci. 82, 4549–4552.
Griffiths, G., Quinn, P., and Warren, G. (1983) Dissection of the Golgi complex 1. Monensin inhibits the transport of viral membrane proteins from medial to trans Golgi cisternae in baby hamster kidney cells infected with semliki forest virus. J. Cell Biol. 96, 835–850.
Hammerschlag, R. (1983) How do neuronal proteins know where they are going? Speculations on the role of molecular address markers. Dev. Neurosci. 6, 2–17.
Hammerschlag, R., Stone, G. C., Bolen, F. A., Lindsey, J., and Ellisman, M. (1982) Evidence that all newly synthesized proteins destined for fast axonal transport pass through the Golgi apparatus. J. Cell Biol. 93, 568–575.
Heifetz, A., Kienan, R. W., and Elbein, A. D. (1979) Mechanisms of action of tunicamycin on the UDPGlc Nac: Dolichyl-phosphate G1cNAc-1-phosphate transferase. Biochem. 18, 2186–2192.
Irwin, C. C. (1985) Comparison of protein synthesis in mitochondria synaptosomes, and intact brain cells. J. Neurochem. 44, 433–438.
Kelly, R. B. (1985) Pathways of protein secretion in eukaryotes. Science 230, 25–32.
Lawrence, J. B. and Singer, R. H. (1986) Intracellular localization of messenger RNAs for cytoskeletal proteins. Cell 45, 407–415.
Lee, K. S., Schottler, F., Oliver, M., and Lynch, G. (1980) Brief bursts of high frequency stimulation produce two types of structural change in rat hippocampus. J. Neurophys. 44, 247–258.
Levinthal, F., Oberdick, J., Yang, S. M., and Levinthal, C. (1987) Specific mRNA identified during development in mouse Purkinje cells and their dendrites. Neurosci. Abs. 13, 1708.
Levy, W. B. and Steward, O. (1979) Synapses as associative memory elements in the hippocampal formation. Brain Res. 175, 233–245.
Lodish, H. V., Kong, N., Snider, M., and Strous, G. J. A. M. (1983) Hepatoma secretory proteins migrate from rough endoplasmic reticulum to Golgi at characteristic rates. Nature 304, 80–83.
Lynch, G. S., Dunwiddie, T., and Gribkoff, V. (1977) Heterosynaptic depression: a postynaptic correlate of long-term potentiation. Nature 266, 737–739.
Matus, A., Bernhardt, R., and Jones, T. H. (1981) High molecular weight microtubule-associated proteins are preferentially associated with dendritic microtubules in brain. Proc. Natl. Acad. Sci. 78, 3010–3014.
McNaughton, B. L., Douglas, R. M., and Goddard, G. V. (1978) Synaptic enhancement in fascia dentata: Cooperativity among coactive afferents. Brain Res. 157, 277–293.
Merlie, J. P. and Sanes, J. R. (1986) Concentration of acetylcholine receptor mRNA in synaptic regions of adult muscle fibers. Nature 317, 66–68.
Morgan, I. G. and Austin, L. (1968) Synaptosomal protein synthesis in a cell-free system. J. Neurochem. 41, 41–51.
Palacios-Pru, E. L., Palacios, L., and Mendoza, R. V. (1981) Synaptogenetic mechanisms during chick cerebellar cortex development. J. Submicrosc. Cytol. 13, 145–167.
Palacios-Pru, E. L., Miranda-Contreras, L., Mendoza, R. V., and Zambrano, E. (1988) Dendritic RNA and postsynaptic density formation in chick cerebellar synaptogenesis. Neurosci. 24, 111–118.
Palade, G. (1965) Intracellular aspects of the process of protein synthesis. Science 189, 347–358.
Peters, A., Palay, S. L., and Webster, de. F. (1976) The Fine Structure of the Nervous System: The Neurons and Supporting Cells. Saunders, Philadelphia, PA.
Phillips, L. L., Chikaraishi, D. M., and Steward, O. (1987) Increases in messenger RNA for actin and tubulin within the denervated neuropil of the dentate gyrus during lesion-induced synaptogenesis. Neurosci. Abs. 13, 1428.
Sedman, G. L., Jeffrey, P. L., Austin, L., and Rostas, J. A. P. (1986) The metabolic turnover of the major proteins of the postsynaptic density. Mol. Bain Res. 1, 221–230.
Simons, K. and Fuller, S. D. (1985), Cell surface polar- ity in epithelia. Ann. Rev. Cell. Biol. 1, 243–288.
Somogyi, P., Smith, A. D., Nunzi, M. G., Gorio, A., Takagi, H., and Wu, J. Y. (1983), Glutamate decarboxylase immunoreactivity in the hippocampus of the cat. Distribution of immunoreactive terminals with special reference to the axon initial segment of pyrimidal neurons. J. Neurosci. 3, 1450–1468.
Spacek, J. (1985) Three-demensional analysis of dendritic spines. II. Spine apparatus and other cytoplasmiccomponents. Anat. Embryo!. 171, 235–243.
Spacek, J. and Hartmann, M. (1983) Three-dimensional analysis of dendritic spines. I. Quantitative observations related to dendritic and synaptic morphology in cerebral and cerebellar cortices. Anat. Embroyl. 167, 289–310.
Stanton, P. K. and Sarvey, J. M. (1983) Blockade of long-term potentiation in rat hippocampal CAl region by inhibitors of protein synthesis. J. Neuro-sci. 4, 3080–3088.
Steward, O. (1983a) Alterations in polyribosomes associated with dendritic spines during the reinnervation of thedentategyrusoftheadultrat. J. Neurosci. 3, 177–188.
Steward, O. (1983b) Polyribosomes at the base of dendritic spines of central nervous system neurons: Their possible role in synapse construction and modification. Cold Spring Harbor Symposia on Quantitiative Biology 48, 745–759.
Steward, O., Davis, L., Reeves, T. M., and Banker, G. (1988) Microcompartmentation of the protein synthetic machinery of neurons: polyribosome localization under postsynaptic sites. Intrinsic Determinants of Neuronal Form and Function(Lasek, R. J., ed.), Liss, NY, pp. 521–544.
Steward, O. and Falk, P. M. (1985) Polyribosomes under developing spine synapses: Growth specializations of dendrites at sites of synaptogenesis. J. Neurosci. Res. 13, 75–88.
Steward, O. and Falk, P. M. (1986) Protein synthetic machinery at postsynaptic sites during synaptogenesis: A quantitative study of the association between polyribosomes and developing synapses. J. Neurosci. 6, 412–423.
Steward, O. and Levy, W. B. (1982) Preferential localization of polyribosomes under the base of dentritic spines in granule cells of the dentate gyrus. J. Neurosci. 2, 284–291.
Steward, O. and Reeves, T. M. (1988) Protein synthetic machinery beneath postsynaptic sites on CNS neurons: Association between polyribosomes and other organelles at the synaptic site. J. Neurosci. 8, 176–184.
Steward, O. and Ribak, C. E. (1986) Polyribosomes associated with synaptic specializations on axon initial segments: Localization of protein synthetic machinery at inhibitory synapses. J. Neurosci. 6, 3079–3085.
Steward, O. and Vinsant, S. V. (1983) The process of reinnervation in the dentate gyrus of the adult rat: A quantitative electron microscopic analysis of terminal proliferation and reactive synaptogenesis. J. Comp. Neurol. 214, 370–386.
Suzuki, K. (1965) The pattern of mammalian brain gangliosides-II. Evaluation of the extraction procedures, postmortem changes, and the effect of formalin preservation. J. Neurochem. 12, 629–638.
Tkacz, J. S. and Lampen, J. O. (1975) Tunicamycin inhibition of polyisoprenyl N-acetylglucosaminyl pyrophosphate formation in calf-liver microsomes. Biochem. Biophys. Res. Commun. 65, 248–257.
Triller, A., Cluzeaud, F., Pfeiffer, F., Betz, H., and Korn, H. (1985) Distribution of glycine receptors at central synapses: An immunoelectron microscopy study. J. Cell Biot. 101, 683–688.
Trimmer, P. A., Phillips, L. L., and Steward, O. (1987) Use of in situhybridization and immunocytochemistry to examine the distribution of actin and tubulin and their messenger RNA in CNS neurons. Neurosci. Abs. 13, 1428.
Verity, M. A. Brown, W. J., and Cheung, M. (1980) Isolation of ribosome containing synaptosome subpopulation with active in vitro protein synthesis. J. Neurosci. Res. 5, 143–153.
Verity, M. A., Brown, W. J., Cheung, M., Huntsman, H., and Smith, R. (1979) Effects of neonatal hypothyroidism on cerebral and cerebellar synaptosome development. J. Neurosci. Res. 2, 323–335.
Walter, P. and Lingappa, V. (1986) Mechanism of protein translocation across the endoplasmic membrane. Ann. Rev. Cell Biol. 2, 499–516.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1989 The Humana Press Inc.
About this chapter
Cite this chapter
Steward, O., Davis, L., Dotti, C., Phillips, L.L., Rao, A., Banker, G. (1989). Protein Synthesis and Processing in Cytoplasmic Microdomains Beneath Postsynaptic Sites on CNS Neurons. In: Bazan, N.G., U’Prichard, D. (eds) Molecular Neurobiology · 1988 ·. Molecular Neurobiology · 1988 ·. Humana Press. https://doi.org/10.1007/978-1-4612-4520-9_9
Download citation
DOI: https://doi.org/10.1007/978-1-4612-4520-9_9
Publisher Name: Humana Press
Print ISBN: 978-1-4612-8857-2
Online ISBN: 978-1-4612-4520-9
eBook Packages: Springer Book Archive