Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 9 April 1993:
Vol. 260. no. 5105, pp. 222 - 226
DOI: 10.1126/science.7682336

Articles

Science, Vol 260, Issue 5105, 222-226
Copyright © 1993 by American Association for the Advancement of Science


articles

Spatially resolved dynamics of cAMP and protein kinase A subunits in Aplysia sensory neurons

BJ Bacskai, B Hochner, M Mahaut-Smith, Adams SR, BK Kaang, ER Kandel, and RY Tsien

Howard Hughes Medical Institute, University of California, San Diego, La Jolla 92093-0647.

Cyclic adenosine monophosphate (cAMP)-dependent protein kinase, labeled with fluorescein and rhodamine on the catalytic and regulatory subunits, respectively, was injected into Aplysia sensory neurons either in culture or in intact cell clusters. Energy transfer between the subunits, a measure of cytosolic cAMP concentration ([cAMP]), and compartmentation of the dissociated subunits were monitored by confocal fluorescence microscopy. Bath application of serotonin produced a much greater elevation of [cAMP] in the processes than in the central bodies of the neurons. The resulting gradients must drive a sizable centripetal flux of cAMP because direct microinjection of cAMP showed that it diffused readily. Perinuclear increases in [cAMP] slowly caused the translocation of the freed catalytic subunit into the nucleus to an extent proportional to the percentage of its dissociation from the regulatory subunit.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Indicators Based on Fluorescence Resonance Energy Transfer (FRET).
R. Y. Tsien (2009)
CSH Protocols 2009, pdb.top57
   Abstract »    Full Text »
Models of Spatially Restricted Biochemical Reaction Systems.
S. R. Neves and R. Iyengar (2009)
J. Biol. Chem. 284, 5445-5449
   Abstract »    Full Text »    PDF »
A Novel Conditional Genetic System Reveals That Increasing Neuronal cAMP Enhances Memory and Retrieval.
C. Isiegas, C. McDonough, T. Huang, R. Havekes, S. Fabian, L.-J. Wu, H. Xu, M.-G. Zhao, J.-I. Kim, Y.-S. Lee, et al. (2008)
J. Neurosci. 28, 6220-6230
   Abstract »    Full Text »    PDF »
Connexin Specificity of Second Messenger Permeation: Real Numbers At Last.
A. L. Harris (2008)
J. Gen. Physiol. 131, 287-292
   Full Text »    PDF »
Alveolar Epithelial 2-Adrenergic Receptors.
G. M. Mutlu and P. Factor (2008)
Am. J. Respir. Cell Mol. Biol. 38, 127-134
   Abstract »    Full Text »    PDF »
Synapsin Regulates Basal Synaptic Strength, Synaptic Depression, and Serotonin-Induced Facilitation of Sensorimotor Synapses in Aplysia.
D. Fioravante, R.-Y. Liu, A. K. Netek, L. J. Cleary, and J. H. Byrne (2007)
J Neurophysiol 98, 3568-3580
   Abstract »    Full Text »    PDF »
Dynamic Regulation, Desensitization, and Cross-talk in Discrete Subcellular Microdomains during beta2-Adrenoceptor and Prostanoid Receptor cAMP Signaling.
D. Willoughby, G. S. Baillie, M. J. Lynch, A. Ciruela, M. D. Houslay, and D. M. F. Cooper (2007)
J. Biol. Chem. 282, 34235-34249
   Abstract »    Full Text »    PDF »
Protein Kinase C Regulates Local Synthesis and Secretion of a Neuropeptide Required for Activity-Dependent Long-Term Synaptic Plasticity.
J.-Y. Hu, Y. Chen, and S. Schacher (2007)
J. Neurosci. 27, 8927-8939
   Abstract »    Full Text »    PDF »
Organization and Ca2+ Regulation of Adenylyl Cyclases in cAMP Microdomains.
D. Willoughby and D. M. F. Cooper (2007)
Physiol Rev 87, 965-1010
   Abstract »    Full Text »    PDF »
Dynamics of Protein Kinase A Signaling at the Membrane, in the Cytosol, and in the Nucleus of Neurons in Mouse Brain Slices.
N. Gervasi, R. Hepp, L. Tricoire, J. Zhang, B. Lambolez, D. Paupardin-Tritsch, and P. Vincent (2007)
J. Neurosci. 27, 2744-2750
   Abstract »    Full Text »    PDF »
Activation of TRPM7 Channels by Phospholipase C-coupled Receptor Agonists.
M. Langeslag, K. Clark, W. H. Moolenaar, F. N. van Leeuwen, and K. Jalink (2007)
J. Biol. Chem. 282, 232-239
   Abstract »    Full Text »    PDF »
Genetically encoded Ca2+ indicators: using genetics and molecular design to understand complex physiology.
M. I. Kotlikoff (2007)
J. Physiol. 578, 55-67
   Abstract »    Full Text »    PDF »
PGE1 stimulation of HEK293 cells generates multiple contiguous domains with different [cAMP]: role of compartmentalized phosphodiesterases.
A. Terrin, G. Di Benedetto, V. Pertegato, Y.-F. Cheung, G. Baillie, M. J. Lynch, N. Elvassore, A. Prinz, F. W. Herberg, M. D. Houslay, et al. (2006)
J. Cell Biol. 175, 441-451
   Abstract »    Full Text »    PDF »
Kinetics of ion channel modulation by cAMP in rat hippocampal neurones.
B. Lancaster, H. Hu, B. Gibb, and J. F. Storm (2006)
J. Physiol. 576, 403-417
   Abstract »    Full Text »    PDF »
Molecular Mechanisms of Memory Storage in Aplysia.
R. D. Hawkins, E. R. Kandel, and C. H. Bailey (2006)
Biol. Bull. 210, 174-191
   Abstract »    Full Text »    PDF »
Essential Role of Somatic and Synaptic Protein Synthesis and Axonal Transport in Long-Term Synapse-Specific Facilitation at Distal Sensorimotor Connections in Aplysia.
X. Guan and G. A. Clark (2006)
Biol. Bull. 210, 238-254
   Abstract »    Full Text »    PDF »
Monitoring of cAMP Synthesis and Degradation in Living Cells.
V. O. Nikolaev and M. J. Lohse (2006)
Physiology 21, 86-92
   Abstract »    Full Text »    PDF »
Soluble Adenylyl Cyclase Reveals the Significance of cAMP Compartmentation on Pulmonary Microvascular Endothelial Cell Barrier.
S. L. Sayner, M. Alexeyev, C. W. Dessauer, and T. Stevens (2006)
Circ. Res. 98, 675-681
   Abstract »    Full Text »    PDF »
Two Signaling Pathways Regulate the Expression and Secretion of a Neuropeptide Required for Long-Term Facilitation in Aplysia.
J.-Y. Hu, F. Wu, and S. Schacher (2006)
J. Neurosci. 26, 1026-1035
   Abstract »    Full Text »    PDF »
An Aplysia Type 4 Phosphodiesterase Homolog Localizes at the Presynaptic Terminals of Aplysia Neuron and Regulates Synaptic Facilitation.
H. Park, J.-A Lee, C. Lee, M.-J. Kim, D.-J. Chang, H. Kim, S.-H. Lee, Y.-S. Lee, and B.-K. Kaang (2005)
J. Neurosci. 25, 9037-9045
   Abstract »    Full Text »    PDF »
Fluorescent indicators of cAMP and Epac activation reveal differential dynamics of cAMP signaling within discrete subcellular compartments.
L. M. DiPilato, X. Cheng, and J. Zhang (2004)
PNAS 101, 16513-16518
   Abstract »    Full Text »    PDF »
Coregulation of Glutamate Uptake and Long-Term Sensitization in Aplysia.
O. Khabour, J. Levenson, L. C. Lyons, L. S. Kategaya, J. Chin, J. H. Byrne, and A. Eskin (2004)
J. Neurosci. 24, 8829-8837
   Abstract »    Full Text »    PDF »
Novel Single Chain cAMP Sensors for Receptor-induced Signal Propagation.
V. O. Nikolaev, M. Bunemann, L. Hein, A. Hannawacker, and M. J. Lohse (2004)
J. Biol. Chem. 279, 37215-37218
   Abstract »    Full Text »    PDF »
Discrete Intracellular Signaling Domains of Soluble Adenylyl Cyclase: Camps of cAMP?.
R. A. Bundey and P. A. Insel (2004)
Sci. STKE 2004, pe19
   Abstract »    Full Text »    PDF »
Bicarbonate-responsive "soluble" adenylyl cyclase defines a nuclear cAMP microdomain.
J. H. Zippin, J. Farrell, D. Huron, M. Kamenetsky, K. C. Hess, D. A. Fischman, L. R. Levin, and J. Buck (2004)
J. Cell Biol. 164, 527-534
   Abstract »    Full Text »    PDF »
Pacemaker channels in mouse thalamocortical neurones are regulated by distinct pathways of cAMP synthesis.
S. G. A. Frere and A. Luthi (2004)
J. Physiol. 554, 111-125
   Abstract »    Full Text »    PDF »
A-kinase anchoring proteins and neuronal signaling mechanisms.
G. K. Carnegie and J. D. Scott (2003)
Genes & Dev. 17, 1557-1568
   Full Text »    PDF »
Redistribution of Syntaxin mRNA in Neuronal Cell Bodies Regulates Protein Expression and Transport during Synapse Formation and Long-Term Synaptic Plasticity.
J.-Y. Hu, X. Meng, and S. Schacher (2003)
J. Neurosci. 23, 1804-1815
   Abstract »    Full Text »    PDF »
Plasticity in Respiratory Motor Control: Invited Review: The crossed phrenic phenomenon: a model for plasticity in the respiratory pathways following spinal cord injury.
H. G. Goshgarian (2003)
J Appl Physiol 94, 795-810
   Abstract »    Full Text »    PDF »
An Extranuclear Locus of cAMP-Dependent Protein Kinase Action Is Necessary and Sufficient for Promotion of Spiral Ganglion Neuronal Survival by cAMP.
J. Bok, X.-M. Zha, Y.-S. Cho, and S. H. Green (2003)
J. Neurosci. 23, 777-787
   Abstract »    Full Text »    PDF »
Coordinate regulation of membrane cAMP by Ca2+-inhibited adenylyl cyclase and phosphodiesterase activities.
J. R. Creighton, N. Masada, D. M. F. Cooper, and T. Stevens (2003)
Am J Physiol Lung Cell Mol Physiol 284, L100-L107
   Abstract »    Full Text »    PDF »
Discrete Microdomains with High Concentration of cAMP in Stimulated Rat Neonatal Cardiac Myocytes.
M. Zaccolo and T. Pozzan (2002)
Science 295, 1711-1715
   Abstract »    Full Text »    PDF »
The many dimensions of cAMP signaling.
J. H. Schwartz (2001)
PNAS 98, 13482-13484
   Full Text »    PDF »
The Molecular Biology of Memory Storage: A Dialogue Between Genes and Synapses.
E. R. Kandel (2001)
Science 294, 1030-1038
   Abstract »    Full Text »    PDF »
Simultaneous measurements of intracellular cAMP and L-type Ca2+ current in single frog ventricular myocytes.
J.-M. Goaillard, P. Vincent, and R. Fischmeister (2001)
J. Physiol. 530, 79-91
   Abstract »    Full Text »    PDF »
A novel function for serotonin-mediated short-term facilitation in Aplysia: Conversion of a transient, cell-wide homosynaptic Hebbian plasticity into a persistent, protein synthesis-independent synapse-specific enhancement.
C. H. Bailey, M. Giustetto, H. Zhu, M. Chen, and E. R. Kandel (2000)
PNAS 97, 11581-11586
   Abstract »    Full Text »    PDF »
Computational Model of the Serotonergic Modulation of Sensory Neurons in Aplysia.
D. A. Baxter, C. C. Canavier, J. W. Clark Jr., and J. H. Byrne (1999)
J Neurophysiol 82, 2914-2935
   Abstract »    Full Text »    PDF »
Enhanced Excitability of Sensory Neurons in Rats With Cutaneous Hyperalgesia Produced by Chronic Compression of the Dorsal Root Ganglion.
J.-M. Zhang, X.-J. Song, and R. H. LaMotte (1999)
J Neurophysiol 82, 3359-3366
   Abstract »    Full Text »    PDF »
Location, location, location: The many addresses of memory formation.
J. C.-P. Yin (1999)
PNAS 96, 9985-9986
   Abstract »    Full Text »    PDF »
Regulation of Synaptic Function by Neurotrophic Factors in Vertebrates and Invertebrates: Implications for Development and Learning.
S. E. McKay, A. L. Purcell, and T. J. Carew (1999)
Learn. Mem. 6, 193-215
   Abstract »    Full Text »
Visualizing Protein-Protein Interactions in the Nucleus of the Living Cell.
R. N. Day, S. K. Nordeen, and Y. Wan (1999)
Mol. Endocrinol. 13, 517-526
   Full Text »
Memory Consolidation for Contextual and Auditory Fear Conditioning Is Dependent on Protein Synthesis, PKA, and MAP Kinase.
G. E. Schafe, N. V. Nadel, G. M. Sullivan, A. Harris, and J. E. LeDoux (1999)
Learn. Mem. 6, 97-110
   Abstract »    Full Text »
Genes to remember.
C. Alberini (1999)
J. Exp. Biol. 202, 2887-2891
   Abstract »    PDF »
Regulation and Immunohistochemical Localization of beta gamma -Stimulated Adenylyl Cyclases in Mouse Hippocampus.
L. P. Baker, M. D. Nielsen, S. Impey, B. M. Hacker, S. W. Poser, M. Y. M. Chan, and D. R. Storm (1999)
J. Neurosci. 19, 180-192
   Abstract »    Full Text »    PDF »
Cloning and Functional Expression of an Aplysia 5-HT Receptor Negatively Coupled to Adenylate Cyclase.
A. Angers, M. V. Storozhuk, T. Duchaine, V. F. Castellucci, and L. DesGroseillers (1998)
J. Neurosci. 18, 5586-5593
   Abstract »    Full Text »    PDF »
Phosphorylation at the Nuclear Localization Signal of Ca2+/Calmodulin-dependent Protein Kinase II Blocks Its Nuclear Targeting.
E. K. Heist, M. Srinivasan, and H. Schulman (1998)
J. Biol. Chem. 273, 19763-19771
   Abstract »    Full Text »    PDF »
Distribution of a Glycosylphosphatidylinositol-anchored Protein at the Apical Surface of MDCK Cells Examined at a Resolution of <100 A Using Imaging Fluorescence Resonance Energy Transfer.
A.K. Kenworthy and M. Edidin (1998)
J. Cell Biol. 142, 69-84
   Abstract »    Full Text »    PDF »
Differential Induction of Long-Term Synaptic Facilitation by Spaced and Massed Applications of Serotonin at Sensory Neuron Synapses of Aplysia californica.
J. Mauelshagen, C. M. Sherff, and T. J. Carew (1998)
Learn. Mem. 5, 246-256
   Abstract »    Full Text »
Binding of Serotonin to Receptors at Multiple Sites Is Required for Structural Plasticity Accompanying Long-Term Facilitation of Aplysia Sensorimotor Synapses.
Z.-Y. Sun and S. Schacher (1998)
J. Neurosci. 18, 3991-4000
   Abstract »    Full Text »    PDF »
Defective Motor Behavior and Neural Gene Expression in RIIbeta -Protein Kinase A Mutant Mice.
E. P. Brandon, S. F. Logue, M. R. Adams, M. Qi, S. P. Sullivan, A. M. Matsumoto, D. M. Dorsa, J. M. Wehner, G. S. McKnight, and R. L. Idzerda (1998)
J. Neurosci. 18, 3639-3649
   Abstract »    Full Text »    PDF »
Long-Term Effects of Axotomy on Excitability and Growth of Isolated Aplysia Sensory Neurons in Cell Culture: Potential Role of cAMP.
S. S. Bedi, A. Salim, S. Chen, and D. L. Glanzman (1998)
J Neurophysiol 79, 1371-1383
   Abstract »    Full Text »    PDF »
Retrograde Signaling in the Development and Modification of Synapses.
R. M. FITZSIMONDS and M.-M. POO (1998)
Physiol Rev 78, 143-170
   Abstract »    Full Text »    PDF »
Role of Calcium-Calmodulin-Dependent Protein Kinase II in Modulation of Sensorimotor Synapses in Aplysia.
K. Nakanishi, F. Zhang, D. A. Baxter, A. Eskin, and J. H. Byrne (1997)
J Neurophysiol 78, 409-416
   Abstract »    Full Text »    PDF »
Visualization of Calcium Influx Through Channels That Shape the Burst and Tonic Firing Modes of Thalamic Relay Cells.
Q. Zhou, D. W. Godwin, D. M. O'Malley, and P. R. Adams (1997)
J Neurophysiol 77, 2816-2825
   Abstract »    Full Text »    PDF »
Pathway-Specific Synaptic Plasticity: Activity-Dependent Enhancement and Suppression of Long-Term Heterosynaptic Facilitation at Converging Inputs on a Single Target.
S. Schacher, F. Wu, and Z.-Y. Sun (1997)
J. Neurosci. 17, 597-606
   Abstract »    Full Text »    PDF »
Differential Effects of 4-Aminopyridine, Serotonin, and Phorbol Esters on Facilitation of Sensorimotor Connections in Aplysia.
S. Sugita, D. A. Baxter, and J. H. Byrne (1997)
J Neurophysiol 77, 177-185
   Abstract »    Full Text »    PDF »
Absence of cerebellar long-term depression in mice lacking neuronal nitric oxide synthase..
V Lev-Ram, Z Nebyelul, M H Ellisman, P L Huang, and R Y Tsien (1997)
Learn. Mem. 4, 169-177
   Abstract »    PDF »
Brief theta-burst stimulation induces a transcription-dependent late phase of LTP requiring cAMP in area CA1 of the mouse hippocampus..
P V Nguyen and E R Kandel (1997)
Learn. Mem. 4, 230-243
   Abstract »    PDF »
Differential Regulation of Type I and Type VIII Ca2+-stimulated Adenylyl Cyclases by Gi-coupled Receptors in Vivo.
M. D. Nielsen, G. C.K. Chan, S. W. Poser, and D. R. Storm (1996)
J. Biol. Chem. 271, 33308-33316
   Abstract »    Full Text »    PDF »
Differential Distribution of Functional Receptors for Neuromodulators Evoking Short-Term Heterosynaptic Plasticity in Aplysia Sensory Neurons.
Z.-Y. Sun, B. Kauderer, and S. Schacher (1996)
J. Neurosci. 16, 7540-7549
   Abstract »    Full Text »    PDF »
Toward a molecular definition of long-term memory storage.
C. H. Bailey, D. Bartsch, and E. R. Kandel (1996)
PNAS 93, 13445-13452
   Abstract »    Full Text »    PDF »
Discovery of genes involved with learning and memory: An experimental synthesis of Hirschian and Benzerian perspectives.
T. Tully (1996)
PNAS 93, 13460-13467
   Abstract »    Full Text »    PDF »
The v-Ki-Ras Oncogene Alters cAMP Nuclear Signaling by Regulating the Location and the Expression of cAMP-dependent Protein Kinase IIbeta.
A. Feliciello, P. Giuliano, A. Porcellini, C. Garbi, S. Obici, E. Mele, E. Angotti, D. Grieco, G. Amabile, S. Cassano, et al. (1996)
J. Biol. Chem. 271, 25350-25359
   Abstract »    Full Text »    PDF »
A Spatial Gradient of Tau Protein Phosphorylation in Nascent Axons.
J. W. Mandell and G. A. Banker (1996)
J. Neurosci. 16, 5727-5740
   Abstract »    Full Text »    PDF »
A Macromolecular Synthesis-Dependent Late Phase of Long-Term Potentiation Requiring cAMP in the Medial Perforant Pathway of Rat Hippocampal Slices.
P. V. Nguyen and E. R. Kandel (1996)
J. Neurosci. 16, 3189-3198
   Abstract »    Full Text »    PDF »
Novel (Rp)-cAMPS Analogs as Tools for Inhibition of cAMP-kinase in Cell Culture.
BjT. Gjertsen, G. Mellgren, A. Otten, E. Maronde, H.-G. Genieser, B. Jastorff, O. K. Vintermyr, G. S. McKnight, and S. O. D (1995)
J. Biol. Chem. 270, 20599-20607
   Abstract »    Full Text »    PDF »
Voltage-sensitive Adenylyl Cyclase Activity in Cultured Neurons.
R. Reddy, D. Smith, G. Wayman, Z. Wu, E. C. Villacres, and D. R. Storm (1995)
J. Biol. Chem. 270, 14340-14346
   Abstract »    Full Text »    PDF »
Role of interneurons in defensive withdrawal reflexes in Aplysia..
L J Cleary, J H Byrne, and W N Frost (1995)
Learn. Mem. 2, 133-151
   PDF »
A uniform extracellular stimulus triggers distinct cAMP signals in different compartments of a simple cell.
T. C. Rich, K. A. Fagan, T. E. Tse, J. Schaack, D. M. F. Cooper, and J. W. Karpen (2001)
PNAS 98, 13049-13054
   Abstract »    Full Text »    PDF »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)