PKA isoforms, neural pathways, and behaviour: Making the connection

Current Opinion in Neurobiology

Volumn 7, Issue 3, 1997, Pages 397-403

  Brandon, Eugene P ^a   Idzerda, Rejean L ^b   McKnight, G Stanley ^b  

^a SALK INSTITUTE FOR BIOLOGICAL STUDIES   (United States)

^b UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIC AMP DEPENDENT PROTEIN KINASE;

BEHAVIOR; BIOCHEMISTRY; CELLULAR DISTRIBUTION; ENZYME ACTIVE SITE; GENE EXPRESSION; MOUSE; NERVE CELL; NERVE CELL PLASTICITY; NERVE TRACT; NONHUMAN; PHYSIOLOGY; PRIORITY JOURNAL; REVIEW; TRANSGENIC MOUSE;

EID: 0030769381     PISSN: 09594388     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-4388(97)80069-4     Document Type: Article

References (62)

1. Doskeland S, Maronde E, Gjertsen BT. The genetic subtypes of cAMP-dependent protein kinase - functionally different or redundant? Biochim Biophys Acta. 1178:1993;249-258.
2. Walsh DA, Van Patten SM. Multiple pathway signal transduction by the cAMP-dependent protein kinase. FASEB J. 8:1994;1227-1236.
3. Mayford M, Abel T, Kandel ER. Transgenic approaches to cognition. Curr Opin Neurobiol. 5:1995;141-148.
4. Grant SG, Silva AJ. Targeting learning. Trends Neurosci. 17:1994;71-75.
5. Brandon EP, Idzerda RL, McKnight GS. Targeting the mouse genome: a compendium of knockout (Part I). Curr Biol. 5:1995;625-634.
6. Brandon EP, Idzerda RL, McKnight GS. Targeting the mouse genome: a compendium of knockout (Part II). Curr Biol. 5:1995;758-765.
7. Brandon EP, Idzerda RL, McKnight GS. Targeting the mouse genome: a compendium of knockout (Part III). Curr Biol. 5:1995;873-881.
8. Capecchi MR. Altering the genome by homologous recombination. Science. 244:1989;1288-1292.
9. McKnight GS, Clegg CH, Uhler MD, Chrivia JC, Cadd GG, Correll LA, Otten AD. Analysis of the cAMP-dependent protein kinase system using molecular genetic approaches. Recent Prog Horm Res. 44:1988;307-335.
10. Cadd G, McKnight GS. Distinct patterns of cAMP-dependent protein kinase gene expression in mouse brain. Neuron. 3:1989;71-79.
11. Uhler MD, McKnight GS. Expression of cDNAs for two isoforms of the catalytic subunit of cAMP-dependent protein kinase. J Biol Chem. 262:1987;15202-15207.
12. Otten AD, McKnight GS. Overexpression of the type II regulatory subunit of the cAMP-dependent protein kinase eliminates the type I holoenzyme in mouse cells. J Biol Chem. 264:1989;20255-20260.
13. Brandon EP, Zhuo M, Huang YY, Qi M, Gerhold KA, Burton KA, Kandel ER, McKnight GS, Idzerda RL. Hippocampal long-term depression and depotentiation are defective in mice carrying a targeted disruption of the gene encoding the RIβ subunit of cAMP-dependent protein kinase. Proc Natl Acad Sci USA. 92:1995;8851-8855 RIβ knockout mice are overtly healthy. They show a compensatory increase in RIα protein, and no change in total brain PKA. Nevertheless, these animals have defects in hippocampal synaptic depression paradigms. This paper also includes a pharmacological demonstration that PKA activity is necessary for hippocampal LTD. of outstanding interest.
14. Cummings DE, Brandon EP, Planas JA, Motamed K, Idzerda RL, McKnight GS. Genetically lean mice result from targeted disruption of the RIIβ subunit of protein kinase A. Nature. 382:1996;622-626 Although not attributed to a neurobiological defect, the RIIβ knockout mice have an increased metabolism and resistance to obesity correlated with an isoform switch of PKA from type II to type I R subunits in adipocytes. of special interest.
15. Amieux PS, Cummings DE, Motamed K, Brandon EP, Wailes LA, Le K, Idzerda RL, McKnight GS. Compensatory regulation of RIα protein levels in protein kinase A mutant mice. J Biol Chem. 272:1997;3993-3998 This paper explores biochemically the compensation by RIα that is observed in various tissues of PKA mutant mice. It is demonstrated that the transcription and translation of RIα mRNA do not change, but, instead, the half-life of the protein is increased. of outstanding interest.
16. Klauck TM, Faux MC, Labudda K, Langeberg LK, Jaken S, Scott JD. Coordination of three signaling enzymes by AKAP79, a mammalian scaffold protein. Science. 271:1996;1589-1592 These investigators find that not only does A-kinase anchoring protein AKAP79 colocalize type II PKA and phosphatase 2B (calcineurin) as described in [15], but this scaffold protein also binds protein kinase C. It is likely that AKAP79 is essential for maintaining this signal transduction complex in certain subcellular locations, including postsynaptic densities. of special interest.
17. Coghlan VM, Perrino BA, Howard M, Langeberg LK, Hicks JB, Gallatin WM, Scott JD. Association of protein kinase A and protein phosphatase 2B with a common anchoring protein. Science. 267:1995;108-111.
18. Faux MC, Scott JD. Molecular glue: kinase anchoring and scaffold proteins. Cell. 85:1996;9-12.
19. Glantz SB, Amat JA, Rubin CS. cAMP signaling in neurons: patterns of neuronal expression and intracellular localization for a novel protein, AKAP 150, that anchors the regulatory subunit of cAMP-dependent protein kinase IIβ Mol Biol Cell. 3:1992;1215-1228.
20. Ludvig N, Ribak CE, Scott JD, Rubin CS. Immunocytochemical localization of the neural-specific regulatory subunit of the type II cyclic AMP-dependent protein kinase to postsynaptic structures in the rat brain. Brain Res. 520:1990;90-102.
21. Skalhegg BS, Tasken K, Hansson V, Huitfeldt HS, Jahnsen T, Lea T. Location of cAMP-dependent protein kinase type I with the TCR-CD3 complex. Science. 263:1994;84-87.
22. Cadd GG, Uhler MD, McKnight GS. Holoenzymes of cAMP-dependent protein kinase containing the neural form of type I regulatory subunit have an increased sensitivity to cyclic nucleotides. J Biol Chem. 265:1990;19502-19506.
23. Solberg R, Tasken K, Wen W, Coghlan VM, Meinkoth JL, Scott JD, Jahnsen T, Taylor SS. Human regulatory subunit RIβ of cAMP-dependent protein kinases: expression, holoenzyme formation and microinjection into living cells. Exp Cell Res. 214:1994;595-605.
24. Gamm DM, Baude EJ, Uhler MD. The major catalytic subunit isoforms of cAMP-dependent protein kinase have distinct biochemical properties in vitro and in vivo. J Biol Chem. 271:1996;15736-15742 Similar to the studies demonstrating the increased cAMP sensitivity of RIβ-containing holoenzyme [20,21], these studies demonstrate that RIIα complexed with Cβ1 has a greater cAMP sensitivity than RIIα complexed with Cα. Moreover, compared to Cα, Cβ1 requires higher concentrations of the protein kinase inhibitors, PKIα and PKIβ1, for inactivation. of special interest.
25. Byrne JH, Kandel ER. Presynaptic facilitation revisited: state and time dependence. J Neurosci. 16:1996;425-435.
26. Kandel ER, Schwartz JH. Molecular biology of learning: modulation of transmitter release. Science. 218:1982;433-443.
27. Drain P, Folkers E, Quinn WG. cAMP-dependent protein kinase and the disruption of learning in transgenic files. Neuron. 6:1991;71-82.
28. Davis RL. Physiology and biochemistry of Drosophila learning mutants. Physiol Rev. 76:1996;299-317.
29. Skoulakis EM, Kalderon D, Davis RL. Preferential expression in mushroom bodies of the catalytic subunit of protein kinase A and its role in learning and memory. Neuron. 11:1993;197-208.
30. Abel T, Nguyen PV, Barad M, Deuel TAS, Kandel ER, Bourtchouladze R. Genetic demonstration of a role for PKA in the late phase of LTP and in hippocampus-based long-term memory. Cell. 88:1997;615-626 This paper directly demonstrates the role of PKA in mammalian learning. Mice expressing the dominant inhibitory subunit of PKA, R(AB), in their hippocampus have a 25% reduction in total hippocampal PKA. Concomitantly, these mice have a significant reduction in the late phase of SC-CA1 LTP, and an inability to translate short-term memories into long-term ones. of outstanding interest.
31. Malenka RC. Synaptic plasticity in the hippocampus: LTP and LTD. Cell. 78:1994;535-538.
32. Bliss TV, Collingridge GL. A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 361:1993;31-39.
33. Bear MF, Abraham WF. Long-term depression in the hippocampus. Annu Rev Neurosci. 19:1996;437-462.
34. Frey U, Huang YY, Kandel ER. Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons. Science. 260:1993;1661-1664.
35. Matthies H, Reymann KG. Protein kinase A inhibitors prevent the maintenance of hippocampal long-term potentiation. Neuroreport. 4:1993;712-714.
36. Weisskopf MG, Castillo PE, Zalutsky RA, Nicoll RA. Mediation of hippocampal mossy fiber long-term potentiation by cyclic AMP. Science. 265:1994;1878-1882.
37. Self DW, Nestler EJ. Molecular mechanisms of drug reinforcement and addiction. Annu Rev Neurosci. 18:1995;463-495.
38. Taiwo YO, Levine JD. Further confirmation of the role of adenyl cyclase and of cAMP-dependent protein kinase in primary afferent hyperalgesia. Neuroscience. 44:1991;131-135.
39. Clegg CH, Cadd GG, McKnight GS. Genetic characterization of a brain-specific form of the type I regulatory subunit of cAMP-dependent protein kinase. Proc Natl Acad Sci USA. 85:1988;3703-3707.
40. Clegg CH, Haugen HS, Boring LF. Promoter sequences in the RIβ subunit gene of cAMP-dependent protein kinase required for transgene expression in mouse brain. J Biol Chem. 271:1996;1638-1644.
41. Massa JS, Walker PS, Moser DR, Fellows RE, Maurer RA. Fetal development and neuronal/glial cell specificity of cAMP-dependent protein kinase subunit mRNAs in rat brain. Dev Neurosci. 13:1991;47-53.
42. Huang Y-Y, Kandel ER, Varshavsky L, Brandon EP, Qi M, Idzerda RL, McKnight GS, Bourtchouladze R. A genetic test of the effects of mutations in PKA on mossy fiber LTP and its relation to spatial and contextual learning. Cell. 83:1995;1211-1222 RIβ and the Cβ1 knockout mice are analyzed electrophysiologically and behaviourally. The authors show that MF - CA3 LTP is severely impaired in both mutants. However, these mice show no defects in spatial learning that correlate with this electrophysiological deficit. In conjunction with other studies examining the relationship between hippocampal plasticity and mnemonic function in mutant mice, it can be concluded that facilitatory plasticity mechanisms at synapses on CA1 neurons are best correlated with spatial learning ability. of outstanding interest.
43. Abeliovich A, Chen C, Goda Y, Silva AJ, Stevens CF, Tonegawa S. Modified hippocampal long-term potentiation in PKCγ-mutant mice. Cell. 75:1993;1253-1262.
44. Abeliovich A, Paylor R, Chen C, Kim JJ, Wehner JM, Tonegawa S. PKCγ mutant mice exhibit mild deficits in spatial and contextual learning. Cell. 75:1993;1263-1271.
45. Silva AJ, Stevens CF, Tonegawa S, Wang Y. Deficient hippocampal long-term potentiation in α-calcium-calmodulin kinase II mutant mice. Science. 257:1992;201-206.
46. Silva AJ, Paylor R, Wehner JM, Tonegawa S. Impaired spatial learning in α-calcium-calmodulin kinase II mutant mice. Science. 257:1992;206-211.
47. Wu ZL, Thomas SA, Villacres EC, Xia Z, Simmons ML, Chavkin C, Palmiter RD, Storm DR. Altered behavior and long-term potentiation in type I adenylyl cyclase mutant mice. Proc Natl Acad Sci USA. 92:1995;220-224 Type 1 adenylyl cyclase knockout mice have dramatic reductions in calcium-stimulated adenylyl cyclase activity in several brain structures, including the hippocampus. Similar to the synapsin II deficient mice studied in [48], they have reduced post-tetanic potentiation, and display altered mnemonic function. of special interest.
48. Bourtchuladze R, Frenguelli B, Blendy J, Cioffi D, Schutz G, Silva AJ. Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell. 79:1994;59-68.
49. Kogan JH, Frankland PW, Blendy JA, Coblentz J, Marowitz Z, Schutz G, Silva AJ. Spaced training induces normal long-term memory in CREB mutant mice. Curr Biol. 7:1997;1-11 Although it was previously demonstrated that mice lacking the α and δ isoforms of cAMP-response element binding protein (CREB) have a profound defect in long-term memory [46], here it is shown that with appropriately spaced training, these mutant mice are able to overcome the defect. Interestingly, these investigators extend the analysis beyond the water maze and fear conditioning to study socially transmitted food preference. This non-spatial task is also dependent upon hippocampal function, and, like the spatial tasks, can only be learned by the CREB mutants if the intertrial interval is of significant duration (>10 minutes). of special interest.
50. Silva AJ, Rosahl TW, Chapman PF, Marowitz Z, Friedman E, Frankland PW, Cestari V, Cioffi D, Sudhof TC, Bourtchuladze R. Impaired learning in mice with abnormal short-lived plasticity. Curr Biol. 6:1996;1509-1518.
51. Nosten-Bertrand M, Errington ML, Murphy KP, Tokugawa Y, Barboni E, Kozlova E, Michalovich D, Morris RG, Silver J, Stewart CL, et al. Normal spatial learning despite regional inhibition of LTP in mice lacking Thy-1. Nature. 379:1996;826-829.
52. Goda Y, Stevens CF. Synaptic plasticity: the basis of particular types of learning. Curr Biol. 6:1996;375-378 A short review describing electrophysiological and behavioural analyses of mutant mice, focusing on the mutants that have not shown obvious correlations between hippocampal plasticity phenomena and mnemonic function. of special interest.
53. Yokoi M, Kobayashi K, Manabe T, Takahashi T, Sakaguchi I, Katsuura G, Shigemoto R, Ohishi H, Nomura S, Nakamura K, et al. Impairment of hippocampal mossy fiber LTD in mice lacking mGluR2. Science. 273:1996;645-647.
54. Motro B, Wojtowicz JM, Bernstein A, van der Kooy D. Steel mutant mice are deficient in hippocampal learning but not long-term potentiation. Proc Natl Acad Sci USA. 93:1996;1808-1813.
55. Glazewski S, Chen CM, Silva A, Fox K. Requirement for α-CaMKII in experience-dependent plasticity of the barrel cortex. Science. 272:1996;421-423.
56. Gordon JA, Cioffi D, Silva AJ, Stryker MP. Deficient plasticity in the primary visual cortex of α-calcium/calmodulin-dependent protein kinase II mutant mice. Neuron. 17:1996;491-499.
57. Gordon JA, Stryker MP. Experience-dependent plasticity of binocular responses in the primary visual cortex of the mouse. J Neurosci. 16:1996;3274-3286 The in vivo paradigm of monocular deprivation during a critical period is believed to provide a valuable model for development of the visual cortex, and has been studied in numerous species, especially cat and ferret. Anticipating the value of genetically modified mice for investigation of the molecular bases of the responses to monocular deprivation, these investigators here characterize the murine version of this paradigm. Even though mice do not have ocular dominance columns,they do have binocular zones containing neurons preferentially driven by one eye or the other, and responses to monocular the murine model will be applicable to this system. of special interest.
58. Beebe SJ, Salomonsky P, Jahnsen T, Li Y. The Cγ subunit is a unique isozyme of the cAMP-dependent protein kinase. J Biol Chem. 267:1992;25505-25512.
59. Qi M, Zhuo M, Skalhegg BS, Brandon EP, Kandel ER, McKnight GS, Idzerda RL. Impaired hippocampal plasticity in mice lacking the Cβ1 catalytic subunit of cAMP-dependent protein kinase. Proc Natl Acad Sci USA. 93:1996;1571-1576 Hippocampal slices from mice lacking Cβ1 show synaptic depression defects similar to those seen in slices from mice lacking RIβ [11]. The one observed difference is that these mice have a defect in their ability to maintain the potentiated response of the SC - CA1 synapse. Because this sustained potentiation is dependent upon gene expression, it is suggested that this specific subunit of PKA may have a critical role in the transcriptional response, possibly in phosphorylation of cAMP-response element binding protein (CREB). of outstanding interest.
60. Nguyen PV, Abel T, Kandel ER. Requirement of a critical period of transcription for induction of a late phase of LTP. Science. 265:1994;1104-1107.
61. Clegg CH, Correll LA, Cadd GG, McKnight GS. Inhibition of intracellular cAMP-dependent protein kinase using mutant genes of the regulatory type I subunit. J Biol Chem. 262:1987;13111-13119.
62. Tsien JZ, Chen DF, Gerber D, Tom C, Mercer EH, Anderson DJ, Mayford M, Kandel ER, Tonegawa S. Subregion- and cell type-restricted gene knockout in mouse brain. Cell. 87:1996;1317-1326 While it had been shown previously that the Cre-IoxP system could be used to mutate specific genes in none-neuronal tissues, here it is demonstrated that this technology is also effective in post-mitotic neurons. These authors take advantage of the locus-dependent expression of α-calcium/calmodulin-dependent protein kinase II (α-CaMKII) promoter-driven Cre recombinase transgenes; with alternative methods of recombinase administration, any gene that has been flanked with loxP sites could, theoretically, be inducibly inactivated with spatial and temporal precision. of outstanding interest.