 |
 Previous Article | Next Article 
Journal of Neuroscience, Vol 9, 4269-4286, Copyright © 1989 by Society for Neuroscience
Neuronal plasminogen activators: cell surface binding sites and involvement in neurite outgrowth
RN Pittman, JK Ivins and HM Buettner
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104.
Sympathetic neurons release both urokinase plasminogen activator (uPA) and
tissue plasminogen activator (tPA). A number of inhibitors of serine
proteases have been tested to determine their effects on neurite outgrowth
from rat sympathetic neurons. Some inhibitors increase neurite outgrowth
while others have little or no effect on outgrowth. Inhibition of
plasminogen activator (PA) activity but not other serine protease activity
correlates with the increase in neurite outgrowth (uPA, r = 0.89; tPA, r =
0.86; plasmin, r = 0.015; thrombin, r = 0.025). Antibodies that inhibit uPA
activity increase neurite outgrowth, while antibodies that bind to uPA but
do not inhibit activity do not alter outgrowth. Time-lapse videomicroscopy
of neurite outgrowth indicates that about 85% of the neurites increase
their rate of outgrowth following exposure to inhibitors of PA. Routinely,
1-2 min after exposure of a growth cone to an inhibitor, there is an
increase in lamellipodial activity at the leading edge of the growth cone
and a decrease in lamellipodial activity on the sides and base of the
growth cone. The increase in the rate of outgrowth combined with the
decrease in lamellipodial activity on the sides of the growth cones results
in neurites being very long and straight in the presence of inhibitors
(persistence time P = 3.7 and 15.3 hr for controls and in the presence of
inhibitors of PA, respectively). PAs released from sympathetic neurons and
PC12 cells interact with 3 different binding sites on the cell surface: (1)
an inhibitor of serine proteases (including uPA and tPA) is bound to the
surface via a heparinase-sensitive site; (2) a uPA- selective binding site
is present in patches on the bottom surface of PC12 cells; and (3) a
tPA-selective binding site with high affinity (KD = 23 +/- 10 nM) and high
capacity (340,000 +/- 130,000 sites/neuron) for 125I-tPA is homogeneously
distributed over the entire surface. Data in the present study are
consistent with PA being involved in neurite outgrowth and open the
possibility of other PA-dependent functions occurring when tPA and/or uPA
interacts with cell surface binding sites.
This article has been cited by other articles:
|
|
|
|
 
U. Schaefer, S. Vorlova, T. Machida, J. P. Melchor, S. Strickland, and R. Levi
Modulation of Sympathetic Activity by Tissue Plasminogen Activator Is Independent of Plasminogen and Urokinase
J. Pharmacol. Exp. Ther.,
July 1, 2007;
322(1):
265 - 273.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. A. Miles, N. M. Andronicos, N. Baik, and R. J. Parmer
Cell-Surface Actin Binds Plasminogen and Modulates Neurotransmitter Release from Catecholaminergic Cells
J. Neurosci.,
December 13, 2006;
26(50):
13017 - 13024.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Perrais, I. C Kleppe, J. W Taraska, and W. Almers
Recapture after exocytosis causes differential retention of protein in granules of bovine chromaffin cells
J. Physiol.,
October 15, 2004;
560(2):
413 - 428.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. W. Seeds, M. E. Basham, and J. E. Ferguson
Absence of Tissue Plasminogen Activator Gene or Activity Impairs Mouse Cerebellar Motor Learning
J. Neurosci.,
August 13, 2003;
23(19):
7368 - 7375.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Barker-Carlson, D. A. Lawrence, and B. S. Schwartz
Acyl-Enzyme Complexes between Tissue-type Plasminogen Activator and Neuroserpin are Short-lived in Vitro
J. Biol. Chem.,
November 27, 2002;
277(49):
46852 - 46857.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. B. Siconolfi and N. W. Seeds
Induction of the Plasminogen Activator System Accompanies Peripheral Nerve Regeneration after Sciatic Nerve Crush
J. Neurosci.,
June 15, 2001;
21(12):
4336 - 4347.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Popa-Wagner, B. Fischer, D. Platt, H. Schmoll, and C. Kessler
Delayed and Blunted Induction of mRNA for Tissue Plasminogen Activator in the Brain of Old Rats Following Pentylenetetrazole-Induced Seizure Activity
J. Gerontol. A Biol. Sci. Med. Sci.,
May 1, 2000;
55(5):
242B - 248.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. Zhuo, D. M. Holtzman, Y. Li, H. Osaka, J. DeMaro, M. Jacquin, and G. Bu
Role of Tissue Plasminogen Activator Receptor LRP in Hippocampal Long-Term Potentiation
J. Neurosci.,
January 15, 2000;
20(2):
542 - 549.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. E. SAKIYAMA, J. C. SCHENSE, and J. A. HUBBELL
Incorporation of heparin-binding peptides into fibrin gels enhances neurite extension: an example of designer matrices in tissue engineering
FASEB J,
December 1, 1999;
13(15):
2214 - 2224.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
J. E. Lochner, M. Kingma, S. Kuhn, C. D. Meliza, B. Cutler, and B. A. Scalettar
Real-Time Imaging of the Axonal Transport of Granules Containing a Tissue Plasminogen Activator/Green Fluorescent Protein Hybrid
Mol. Biol. Cell,
September 1, 1998;
9(9):
2463 - 2476.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
C. Shimizu, S. Yoshida, M. Shibata, K. Kato, Y. Momota, K. Matsumoto, T. Shiosaka, R. Midorikawa, T. Kamachi, A. Kawabe, et al.
Characterization of Recombinant and Brain Neuropsin, a Plasticity-related Serine Protease
J. Biol. Chem.,
May 1, 1998;
273(18):
11189 - 11196.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z.-L. Chen, Y. Momota, K. Kato, M. Taniguchi, N. Inoue, S. Shiosaka, and S. Yoshida
Expression of Neuropsin mRNA in the Mouse Embryo and the Pregnant Uterus
J. Histochem. Cytochem.,
March 1, 1998;
46(3):
313 - 320.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. R. Krueger, G.-P. Ghisu, P. Cinelli, T. P. Gschwend, T. Osterwalder, D. P. Wolfer, and P. Sonderegger
Expression of Neuroserpin, an Inhibitor of Tissue Plasminogen Activator, in the Developing and Adult Nervous System of the Mouse
J. Neurosci.,
December 1, 1997;
17(23):
8984 - 8996.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Parmer, M. Mahata, S. Mahata, M. T. Sebald, D. T. O'Connor, and L. A. Miles
Tissue Plasminogen Activator (t-PA) Is Targeted to the Regulated Secretory Pathway. CATECHOLAMINE STORAGE VESICLES AS A RESERVOIR FOR THE RAPID RELEASE OF t-PA
J. Biol. Chem.,
January 17, 1997;
272(3):
1976 - 1982.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. W. Seeds, B. L. Williams, and P. C. Bickford
Tissue Plasminogen Activator Induction in Purkinje Neurons After Cerebellar Motor Learning
Science,
December 22, 1995;
270(5244):
1992 - 1994.
[Abstract]
[PDF]
|
|
|
|
|
|
|
E. Watanabe, N. Maeda, F. Matsui, Y. Kushima, M. Noda, and A. Oohira
Neuroglycan C, a Novel Membrane-spanning Chondroitin Sulfate Proteoglycan That Is Restricted to the Brain
J. Biol. Chem.,
November 10, 1995;
270(45):
26876 - 26882.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Carroll, S. Tsirka, W. Richards, M. Frohman, and S Strickland
The mouse tissue plasminogen activator gene 5' flanking region directs appropriate expression in development and a seizure-enhanced response in the CNS
Development,
January 11, 1994;
120(11):
3173 - 3183.
[Abstract]
[PDF]
|
|
|
|
|
|
|
I. M. Mansuy, H. van der Putten, P. Schmid, M. Meins, F. M. Botteri, and D. Monard
Variable and multiple expression of Protease Nexin-1 during mouse organogenesis and nervous system development
Development,
December 1, 1993;
119(4):
1119 - 1134.
[Abstract]
[PDF]
|
|
|
|
|
|
|
L. Fessler, M. Condic, R. Nelson, J. Fessler, and J. Fristrom
Site-specific cleavage of basement membrane collagen IV during Drosophila metamorphosis
Development,
January 3, 1993;
117(3):
1061 - 1069.
[Abstract]
[PDF]
|
|
|
|
|
|
|
Y Sumi, M. Dent, D. Owen, P. Seeley, and R. Morris
The expression of tissue and urokinase-type plasminogen activators in neural development suggests different modes of proteolytic involvement in neuronal growth
Development,
January 11, 1992;
116(3):
625 - 637.
[Abstract]
[PDF]
|
|
|
|
|
|
|
A. T. Jacovina, F. Zhong, E. Khazanova, E. Lev, A. B. Deora, and K. A. Hajjar
Neuritogenesis and the Nerve Growth Factor-induced Differentiation of PC-12 Cells Requires Annexin II-mediated Plasmin Generation
J. Biol. Chem.,
December 21, 2001;
276(52):
49350 - 49358.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
