Abstract
The subcellular distribution of Proteins Ia and Ib, two proteins which serve as specific substrates for protein kinases present in mammalian brain, was studied in the dog cerebral cortex. Proteins Ia and Ib were found to be most highly enriched in synaptic vesicle fractions; they were also present in postsynaptic density and synaptic membrane fractions in significant amounts. Proteins Ia and Ib present in the synaptic vesicle fraction appear to be similar, if not identical, to those present in the postsynaptic density fraction as judged by several criteria: (a) the ability to serve as substrate for cAMP-dependent protein kinase, (b) electrophoretic mobility in the presence of sodium dodecyl sulfate, (c) extractability with NH4Cl or EGTA, and (d) fragmentation to electrophoretically similar peptides by a purified Staphylococcus aureus protease. In addition, the postsynaptic density fraction has been found to contain cAMP-dependent Protein Ia and Protein Ib kinase activity. The subcellular localization of Proteins Ia and Ib suggests a role for these proteins in the physiology of the synapse.
Full Text
The Full Text of this article is available as a PDF (1.0 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bloom F. E. The role of cyclic nucleotides in central synaptic function. Rev Physiol Biochem Pharmacol. 1975;74:1–103. doi: 10.1007/3-540-07483-x_19. [DOI] [PubMed] [Google Scholar]
- Cohen R. S., Blomberg F., Berzins K., Siekevitz P. The structure of postsynaptic densities isolated from dog cerebral cortex. I. Overall morphology and protein composition. J Cell Biol. 1977 Jul;74(1):181–203. doi: 10.1083/jcb.74.1.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cotman C. W., Banker G., Churchill L., Taylor D. Isolation of postsynaptic densities from rat brain. J Cell Biol. 1974 Nov;63(2 Pt 1):441–455. doi: 10.1083/jcb.63.2.441. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Daly J. W. The formation, degradation, and function of cyclic nucleotides in the nervous system. Int Rev Neurobiol. 1977;20:105–168. doi: 10.1016/s0074-7742(08)60652-2. [DOI] [PubMed] [Google Scholar]
- Drummond G. I. Metabolism and functions of cyclic AMP in nerve. Prog Neurobiol. 1973;2(2):119–176. doi: 10.1016/0301-0082(73)90001-4. [DOI] [PubMed] [Google Scholar]
- Feit H., Neudeck U., Shay J. Anomalous electrophoretic properties of brain filament protein subunits. Brain Res. 1977 Sep 16;133(2):341–349. doi: 10.1016/0006-8993(77)90769-7. [DOI] [PubMed] [Google Scholar]
- Greengard P., Kebabian J. W. Role of cyclic AMP in synaptic transmission in the mammalian peripheral nervous system. Fed Proc. 1974 Apr;33(4):1059–1067. [PubMed] [Google Scholar]
- Greengard P. Possible role for cyclic nucleotides and phosphorylated membrane proteins in postsynaptic actions of neurotransmitters. Nature. 1976 Mar 11;260(5547):101–108. doi: 10.1038/260101a0. [DOI] [PubMed] [Google Scholar]
- Gurd J. W., Jones L. R., Mahler H. R., Moore W. J. Isolation and partial characterization of rat brain synaptic plasma membranes. J Neurochem. 1974 Feb;22(2):281–290. doi: 10.1111/j.1471-4159.1974.tb11591.x. [DOI] [PubMed] [Google Scholar]
- Jones D. H., Matus A. I. Isolation of synaptic plasma membrane from brain by combined flotation-sedimentation density gradient centrifugation. Biochim Biophys Acta. 1974 Aug 9;356(3):276–287. doi: 10.1016/0005-2736(74)90268-5. [DOI] [PubMed] [Google Scholar]
- Krebs E. G. Protein kinases. Curr Top Cell Regul. 1972;5:99–133. [PubMed] [Google Scholar]
- Krueger B. K., Forn J., Greengard P. Depolarization-induced phosphorylation of specific proteins, mediated by calcium ion influx, in rat brain synaptosomes. J Biol Chem. 1977 Apr 25;252(8):2764–2773. [PubMed] [Google Scholar]
- Langan T. A. Protein kinases and protein kinase substrates. Adv Cyclic Nucleotide Res. 1973;3:99–153. [PubMed] [Google Scholar]
- Lohmann S. M., Ueda T., Greengard P. Ontogeny of synaptic phosphoproteins in brain. Proc Natl Acad Sci U S A. 1978 Aug;75(8):4037–4041. doi: 10.1073/pnas.75.8.4037. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Matus A. I., Taff-Jones D. H. Morphology and molecular composition of isolated postsynaptic junctional structures. Proc R Soc Lond B Biol Sci. 1978 Dec 4;203(1151):135–151. doi: 10.1098/rspb.1978.0097. [DOI] [PubMed] [Google Scholar]
- Morgan I. G., Vincendon G., Gombos G. Adult rat brain synaptic vesicles. I. Isolation and characterization. Biochim Biophys Acta. 1973 Oct 5;320(3):671–680. doi: 10.1016/0304-4165(73)90147-5. [DOI] [PubMed] [Google Scholar]
- Rubin C. S., Rosen O. M. Protein phosphorylation. Annu Rev Biochem. 1975;44:831–887. doi: 10.1146/annurev.bi.44.070175.004151. [DOI] [PubMed] [Google Scholar]
- Ueda T., Greengard P. Adenosine 3':5'-monophosphate-regulated phosphoprotein system of neuronal membranes. I. Solubilization, purification, and some properties of an endogenous phosphoprotein. J Biol Chem. 1977 Jul 25;252(14):5155–5163. [PubMed] [Google Scholar]
- Ueda T., Maeno H., Greengard P. Regulation of endogenous phosphorylation of specific proteins in synaptic membrane fractions from rat brain by adenosine 3':5'-monophosphate. J Biol Chem. 1973 Dec 10;248(23):8295–8305. [PubMed] [Google Scholar]
- Walter U., Greengard P. Quantitative labeling of the regulatory subunit of type II cAMP-dependent protein kinase from bovine heart by a photoaffinity analog. J Cyclic Nucleotide Res. 1978 Dec;4(6):437–444. [PubMed] [Google Scholar]
- Walter U., Kanof P., Schulman H., Greengard P. Adenosine 3':5'-monophosphate receptor proteins in mammalian brain. J Biol Chem. 1978 Sep 10;253(17):6275–6280. [PubMed] [Google Scholar]
- Weller M., Morgan I. G. Localization in the synaptic junction of the cyclic AMP stimulated intrinsic protein kinase activity of synaptosomal plasma membranes. Biochim Biophys Acta. 1976 Apr 16;433(1):223–227. doi: 10.1016/0005-2736(76)90190-5. [DOI] [PubMed] [Google Scholar]
- Whittaker V. P., Michaelson I. A., Kirkland R. J. The separation of synaptic vesicles from nerve-ending particles ('synaptosomes'). Biochem J. 1964 Feb;90(2):293–303. doi: 10.1042/bj0900293. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wolfe L. S., Morgan I. G., Gombos G. Isolation of plasma membranes from rat brain. Biochim Biophys Acta. 1971 Sep 14;241(3):737–751. doi: 10.1016/0005-2736(71)90002-2. [DOI] [PubMed] [Google Scholar]
