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.


Science 22 December 1995:
Vol. 270. no. 5244, pp. 1992 - 1994
DOI: 10.1126/science.270.5244.1992

Reports

Tissue Plasminogen Activator Induction in Purkinje Neurons After Cerebellar Motor Learning

Nicholas W. Seeds (1),  Brian L. Williams,  Paula C. Bickford

The cerebellar cortex is implicated in the learning of complex motor skills. This learning may require synaptic remodeling of Purkinje cell inputs. An extracellular serine protease, tissue plasminogen activator (tPA), is involved in remodeling various nonneural tissues and is associated with developing and regenerating neurons. In situ hybridization showed that expression of tPA messenger RNA was increased in the Purkinje neurons of rats within an hour of their being trained for a complex motor task. Antibody to tPA also showed the induction of tPA protein associated with cerebellar Purkinje cells. Thus, the induction of tPA during motor learning may play a role in activity-dependent synaptic plasticity.


N. W. Seeds, Neuroscience Program and Department of Biochemistry/Biophysics and Genetics, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
B. L. Williams, Medical Scientist Training Program, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
P. C. Bickford, Department of Pharmacology and Veterans Administration Medical Center, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
(1) To whom correspondence should be addressed.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The Function of Activity-Regulated Genes in the Nervous System.
S. Loebrich and E. Nedivi (2009)
Physiol Rev 89, 1079-1103
   Abstract »    Full Text »    PDF »
The Low-Density Lipoprotein Receptor-Related Protein 1 Mediates Tissue-Type Plasminogen Activator-Induced Microglial Activation in the Ischemic Brain.
C. Zhang, J. An, D. K. Strickland, and M. Yepes (2009)
Am. J. Pathol. 174, 586-594
   Abstract »    Full Text »    PDF »
Tissue-Type Plasminogen Activator and the Low-Density Lipoprotein Receptor-Related Protein Mediate Cerebral Ischemia-Induced Nuclear Factor-{kappa}B Pathway Activation.
X. Zhang, R. Polavarapu, H. She, Z. Mao, and M. Yepes (2007)
Am. J. Pathol. 171, 1281-1290
   Abstract »    Full Text »    PDF »
Tissue-type plasminogen activator-mediated shedding of astrocytic low-density lipoprotein receptor-related protein increases the permeability of the neurovascular unit.
R. Polavarapu, M. C. Gongora, H. Yi, S. Ranganthan, D. A. Lawrence, D. Strickland, and M. Yepes (2007)
Blood 109, 3270-3278
   Abstract »    Full Text »    PDF »
Neural stem cells rescue nervous purkinje neurons by restoring molecular homeostasis of tissue plasminogen activator and downstream targets..
J. Li, J. Imitola, E. Y. Snyder, and R. L. Sidman (2006)
J. Neurosci. 26, 7839-7848
   Abstract »    Full Text »    PDF »
Purkinje neuron degeneration in nervous (nr) mutant mice is mediated by a metabolic pathway involving excess tissue plasminogen activator.
J. Li, Y. Ma, Y. D. Teng, K. Zheng, T. K. Vartanian, E. Y. Snyder, and R. L. Sidman (2006)
PNAS 103, 7847-7852
   Abstract »    Full Text »    PDF »
Expression of Neuroserpin Is Linked to Neuroendocrine Cell Activation.
D. M. de Groot and G. J. M. Martens (2005)
Endocrinology 146, 3791-3799
   Abstract »    Full Text »    PDF »
Plasminogen activators promote excitotoxicity-induced retinal damage.
R. S. Mali, M. Cheng, and S. K. Chintala (2005)
FASEB J 19, 1280-1289
   Abstract »    Full Text »    PDF »
Vampire Bat Salivary Plasminogen Activator (Desmoteplase) Inhibits Tissue-Type Plasminogen Activator-Induced Potentiation of Excitotoxic Injury.
C. Reddrop, R. X. Moldrich, P. M. Beart, M. Farso, G. T. Liberatore, D. W. Howells, K.-U. Petersen, W.-D. Schleuning, and R. L. Medcalf (2005)
Stroke 36, 1241-1246
   Abstract »    Full Text »    PDF »
From The Cover: Ethanol-withdrawal seizures are controlled by tissue plasminogen activator via modulation of NR2B-containing NMDA receptors.
R. Pawlak, J. P. Melchor, T. Matys, A. E. Skrzypiec, and S. Strickland (2005)
PNAS 102, 443-448
   Abstract »    Full Text »    PDF »
Arginine 260 of the Amino-terminal Domain of NR1 Subunit Is Critical for Tissue-type Plasminogen Activator-mediated Enhancement of N-Methyl-D-aspartate Receptor Signaling.
M. Fernandez-Monreal, J. P. Lopez-Atalaya, K. Benchenane, M. Cacquevel, F. Dulin, J.-P. Le Caer, J. Rossier, A.-C. Jarrige, E. T. MacKenzie, N. Colloc'h, et al. (2004)
J. Biol. Chem. 279, 50850-50856
   Abstract »    Full Text »    PDF »
New Functions for an Old Enzyme: Nonhemostatic Roles for Tissue-Type Plasminogen Activator in the Central Nervous System.
M. Yepes and D. A. Lawrence (2004)
Experimental Biology and Medicine 229, 1097-1104
   Abstract »    Full Text »    PDF »
Regulation of Brain Proteolytic Activity Is Necessary for the In Vivo Function of NMDA Receptors.
M. Kvajo, H. Albrecht, M. Meins, U. Hengst, E. Troncoso, S. Lefort, J. Z. Kiss, C. C. H. Petersen, and D. Monard (2004)
J. Neurosci. 24, 9734-9743
   Abstract »    Full Text »    PDF »
From The Cover: The tissue plasminogen activator-plasmin system participates in the rewarding effect of morphine by regulating dopamine release.
T. Nagai, K. Yamada, M. Yoshimura, K. Ishikawa, Y. Miyamoto, K. Hashimoto, Y. Noda, A. Nitta, and T. Nabeshima (2004)
PNAS 101, 3650-3655
   Abstract »    Full Text »    PDF »
The Low Density Lipoprotein Receptor-related Protein Modulates Protease Activity in the Brain by Mediating the Cellular Internalization of Both Neuroserpin and Neuroserpin-Tissue-type Plasminogen Activator Complexes.
A. Makarova, I. Mikhailenko, T. H. Bugge, K. List, D. A. Lawrence, and D. K. Strickland (2003)
J. Biol. Chem. 278, 50250-50258
   Abstract »    Full Text »    PDF »
Absence of Tissue Plasminogen Activator Gene or Activity Impairs Mouse Cerebellar Motor Learning.
N. W. Seeds, M. E. Basham, and J. E. Ferguson (2003)
J. Neurosci. 23, 7368-7375
   Abstract »    Full Text »    PDF »
Cell Type-Specific Roles for Tissue Plasminogen Activator Released by Neurons or Microglia after Excitotoxic Injury.
C.-J. Siao, S. R. Fernandez, and S. E. Tsirka (2003)
J. Neurosci. 23, 3234-3242
   Abstract »    Full Text »    PDF »
Partial rescue of neural apoptosis in the Lurcher mutant mouse through elimination of tissue plasminogen activator.
W. Lu and S. E. Tsirka (2003)
Development 129, 2043-2050
   Abstract »    Full Text »    PDF »
Vampire Bat Salivary Plasminogen Activator (Desmoteplase): A Unique Fibrinolytic Enzyme That Does Not Promote Neurodegeneration.
G. T. Liberatore, A. Samson, C. Bladin, W.-D. Schleuning, and R. L. Medcalf (2003)
Stroke 34, 537-543
   Abstract »    Full Text »    PDF »
Involvement of Tissue Plasminogen Activator in Onset and Effector Phases of Experimental Allergic Encephalomyelitis.
W. Lu, M. Bhasin, and S. E. Tsirka (2002)
J. Neurosci. 22, 10781-10789
   Abstract »    Full Text »    PDF »
Truncating Neurotrypsin Mutation in Autosomal Recessive Nonsyndromic Mental Retardation.
F. Molinari, M. Rio, V. Meskenaite, F. Encha-Razavi, J. Auge, D. Bacq, S. Briault, M. Vekemans, A. Munnich, T. Attie-Bitach, et al. (2002)
Science 298, 1779-1781
   Abstract »    Full Text »    PDF »
Permissive proteolytic activity for visual cortical plasticity.
N. Mataga, N. Nagai, and T. K. Hensch (2002)
PNAS 99, 7717-7721
   Abstract »    Full Text »    PDF »
Mutant Neuroserpin (S49P) That Causes Familial Encephalopathy with Neuroserpin Inclusion Bodies Is a Poor Proteinase Inhibitor and Readily Forms Polymers in Vitro.
D. Belorgey, D. C. Crowther, R. Mahadeva, and D. A. Lomas (2002)
J. Biol. Chem. 277, 17367-17373
   Abstract »    Full Text »    PDF »
Coordinated Induction of Extracellular Proteolysis Systems During Experimental Autoimmune Encephalomyelitis in Mice.
T. Teesalu, A. E. Hinkkanen, and A. Vaheri (2001)
Am. J. Pathol. 159, 2227-2237
   Abstract »    Full Text »    PDF »
Experience-Dependent Gene Expression in the Rat Hippocampus after Spatial Learning: A Comparison of the Immediate-Early Genes Arc, c-fos, and zif268.
J. F. Guzowski, B. Setlow, E. K. Wagner, and J. L. McGaugh (2001)
J. Neurosci. 21, 5089-5098
   Abstract »    Full Text »    PDF »
Cerebellar Long-Term Depression: Characterization, Signal Transduction, and Functional Roles.
M. Ito (2001)
Physiol Rev 81, 1143-1195
   Abstract »    Full Text »    PDF »
Neuroserpin reduces cerebral infarct volume and protects neurons from ischemia-induced apoptosis.
M. Yepes, M. Sandkvist, M. K. K. Wong, T. A. Coleman, E. Smith, S. L. Cohan, and D. A. Lawrence (2000)
Blood 96, 569-576
   Abstract »    Full Text »    PDF »
Delayed and Blunted Induction of mRNA for Tissue Plasminogen Activator in the Brain of Old Rats Following Pentylenetetrazole-Induced Seizure Activity.
A. Popa-Wagner, B. Fischer, D. Platt, H. Schmoll, and C. Kessler (2000)
J. Gerontol. A Biol. Sci. Med. Sci. 55, 242B-248
   Abstract »    Full Text »
The Tissue Plasminogen Activator (Tpa/Plasmin) Extracellular Proteolytic System Regulates Seizure-Induced Hippocampal Mossy Fiber Outgrowth through a Proteoglycan Substrate.
Y. P. Wu, C.-J. Siao, W. Lu, T.-C. Sung, M. A. Frohman, P. Milev, T. H. Bugge, J. L. Degen, J. M. Levine, R. U. Margolis, et al. (2000)
J. Cell Biol. 148, 1295-1304
   Abstract »    Full Text »    PDF »
Neuronal migration is retarded in mice lacking the tissue plasminogen activator gene.
N. W. Seeds, M. E. Basham, and S. P. Haffke (1999)
PNAS 96, 14118-14123
   Abstract »    Full Text »    PDF »
Tissue Plasminogen Activator (tPA) Deficiency Exacerbates Cerebrovascular Fibrin Deposition and Brain Injury in a Murine Stroke Model : Studies in tPA-Deficient Mice and Wild-Type Mice on a Matched Genetic Background.
P. Tabrizi, L. Wang, N. Seeds, J. G. McComb, S. Yamada, J. H. Griffin, P. Carmeliet, M. H. Weiss, and B. V. Zlokovic (1999)
Arterioscler Thromb Vasc Biol 19, 2801-2806
   Abstract »    Full Text »    PDF »
Transforming growth factor-{beta}1 as a regulator of the serpins/t-PA axis in cerebral ischemia.
F. DOCAGNE, O. NICOLE, H. H. MARTI, E. T. MacKENZIE, A. BUISSON, and D. VIVIEN (1999)
FASEB J 13, 1315-1324
   Abstract »    Full Text »
Spatiotemporal Expression Patterns of Metalloproteinases and Their Inhibitors in the Postnatal Developing Rat Cerebellum.
C. Vaillant, M. Didier-Bazes, A. Hutter, M.-F. Belin, and N. Thomasset (1999)
J. Neurosci. 19, 4994-5004
   Abstract »    Full Text »    PDF »
Up-regulation of a serine protease inhibitor in astrocytes mediates the neuroprotective activity of transforming growth factor ß1.
A. Buisson, O. Nicole, F. Docagne, H. Sartelet, E. T. Mackenzie, and D. Vivien (1998)
FASEB J 12, 1683-1691
   Abstract »    Full Text »
The Low Density Lipoprotein Receptor Gene Family. DIFFERENTIAL EXPRESSION OF TWO alpha 2-MACROGLOBULIN RECEPTORS IN THE BRAIN.
W. Stockinger, E. Hengstschlager-Ottnad, S. Novak, A. Matus, M. Huttinger, J. Bauer, H. Lassmann, W. J. Schneider, and J. Nimpf (1998)
J. Biol. Chem. 273, 32213-32221
   Abstract »    Full Text »    PDF »
Serine Proteases in Rodent Hippocampus.
B. J. Davies, B. S. Pickard, M. Steel, R. G. M. Morris, and R. Lathe (1998)
J. Biol. Chem. 273, 23004-23011
   Abstract »    Full Text »    PDF »
Real-Time Imaging of the Axonal Transport of Granules Containing a Tissue Plasminogen Activator/Green Fluorescent Protein Hybrid.
J. E. Lochner, M. Kingma, S. Kuhn, C. D. Meliza, B. Cutler, and B. A. Scalettar (1998)
Mol. Biol. Cell 9, 2463-2476
   Abstract »    Full Text »
Extrahepatic Expression and Regulation of Protein C in the Mouse.
K. Yamamoto and D. J. Loskutoff (1998)
Am. J. Pathol. 153, 547-555
   Abstract »    Full Text »    PDF »
Spatial Memory and Learning in Transgenic Mice: Fact or Artifact?.
D. P. Wolfer, M. Stagljar-Bozicevic, M. L. Errington, and H.-P. Lipp (1998)
Physiology 13, 118-123
   Abstract »    Full Text »    PDF »
The Axonally Secreted Serine Proteinase Inhibitor, Neuroserpin, Inhibits Plasminogen Activators and Plasmin but Not Thrombin.
T. Osterwalder, P. Cinelli, A. Baici, A. Pennella, S. R. Krueger, S. P. Schrimpf, M. Meins, and P. Sonderegger (1998)
J. Biol. Chem. 273, 2312-2321
   Abstract »    Full Text »    PDF »
Neuroserpin, a Brain-associated Inhibitor of Tissue Plasminogen Activator Is Localized Primarily in Neurons. IMPLICATIONS FOR THE REGULATION OF MOTOR LEARNING AND NEURONAL SURVIVAL.
G. A. Hastings, T. A. Coleman, C. C. Haudenschild, S. Stefansson, E. P. Smith, R. Barthlow, S. Cherry, M. Sandkvist, and D. A. Lawrence (1997)
J. Biol. Chem. 272, 33062-33067
   Abstract »    Full Text »    PDF »
Expression of Neuroserpin, an Inhibitor of Tissue Plasminogen Activator, in the Developing and Adult Nervous System of the Mouse.
S. R. Krueger, G.-P. Ghisu, P. Cinelli, T. P. Gschwend, T. Osterwalder, D. P. Wolfer, and P. Sonderegger (1997)
J. Neurosci. 17, 8984-8996
   Abstract »    Full Text »    PDF »
Nervous System-Specific Expression of a Novel Serine Protease: Regulation in the Adult Rat Spinal Cord by Excitotoxic Injury.
I. A. Scarisbrick, M. D. Towner, and P. J. Isackson (1997)
J. Neurosci. 17, 8156-8168
   Abstract »    Full Text »    PDF »
Optimal Subsite Occupancy and Design of a Selective Inhibitor of Urokinase.
S.-H. Ke, G. S. Coombs, K. Tachias, D. R. Corey, and E. L. Madison (1997)
J. Biol. Chem. 272, 20456-20462
   Abstract »    Full Text »    PDF »
Neural Correlates of Motor Memory Consolidation.
R. Shadmehr and H. H. Holcomb (1997)
Science 277, 821-825
   Abstract »    Full Text »
Distinguishing the Specificities of Closely Related Proteases. ROLE OF P3 IN SUBSTRATE AND INHIBITOR DISCRIMINATION BETWEEN TISSUE-TYPE PLASMINOGEN ACTIVATOR AND UROKINASE.
S.-H. Ke, G. S. Coombs, K. Tachias, M. Navre, D. R. Corey, and E. L. Madison (1997)
J. Biol. Chem. 272, 16603-16609
   Abstract »    Full Text »    PDF »
Endogenous Serine Protease Inhibitor Modulates Epileptic Activity and Hippocampal Long-Term Potentiation.
A. Luthi, H. v. d. Putten, F. M. Botteri, I. M. Mansuy, M. Meins, U. Frey, G. Sansig, C. Portet, M. Schmutz, M. Schroder, et al. (1997)
J. Neurosci. 17, 4688-4699
   Abstract »    Full Text »    PDF »
Functional Stages in the Formation of Human Long-Term Motor Memory.
R. Shadmehr and T. Brashers-Krug (1997)
J. Neurosci. 17, 409-419
   Abstract »    Full Text »    PDF »
The cell surface metalloprotease/disintegrin Kuzbanian is required for axonal extension in Drosophila.
D. Fambrough, D. Pan, G. M. Rubin, and C. S. Goodman (1996)
PNAS 93, 13233-13238
   Abstract »    Full Text »    PDF »
Extracellular Proteases in Neuronal Function and Degeneration.
S. Strickland, A. Gualandris, A.D. Rogove, and S.E. Tsirka (1996)
Cold Spring Harb Symp Quant Biol 61, 739-745
   Abstract »    PDF »
Neuritogenesis and the Nerve Growth Factor-induced Differentiation of PC-12 Cells Requires Annexin II-mediated Plasmin Generation.
A. T. Jacovina, F. Zhong, E. Khazanova, E. Lev, A. B. Deora, and K. A. Hajjar (2001)
J. Biol. Chem. 276, 49350-49358
   Abstract »    Full Text »    PDF »



To Advertise     Find Products


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