 |
Previous Article | Next Article 
The Journal of Neuroscience, February 1, 2002, 22(3):931-945
Mechanisms of the Release of Anterogradely Transported
Neurotrophin-3 from Axon Terminals
XiaoXia
Wang1,
Rafal
Butowt1,
Michael R.
Vasko2, and
Christopher S.
von
Bartheld1
1 Department of Physiology and Cell Biology, University
of Nevada School of Medicine, Reno, Nevada 89557, and
2 Department of Pharmacology and Toxicology, University of
Indiana School of Medicine, Indianapolis, Indiana 46202-5120
Neurotrophins have profound effects on synaptic function and
structure. They can be derived from presynaptic, as well as
postsynaptic, sites. To date, it has not been possible to measure the
release of neurotrophins from axon terminals in intact tissue. We
implemented a novel, extremely sensitive assay for the release and
transfer of anterogradely transported neurotrophin-3 (NT-3) from a
presynaptic to a postsynaptic location that uses synaptosomal
fractionation after introduction of radiolabeled NT-3 into the
retinotectal projection of chick embryos. Release of the anterogradely
transported NT-3 in intact tissue was assessed by measuring the amount
remaining in synaptosomal preparations after treatment of whole tecta
with pharmacological agents. Use of this assay reveals that release of
NT-3 from axon terminals is increased by depolarization, calcium influx
via N-type calcium channels, and cAMP analogs, and release is most
profoundly increased by excitation with kainic acid or mobilization of
calcium from intracellular stores. NT-3 release depends on
extracellular sodium, CaM kinase II activity, and requires intact
microtubules and microfilaments. Dantrolene inhibits the high
potassium-induced release of NT-3, indicating that release of calcium
from intracellular stores is required. Tetanus toxin also inhibits NT-3
release, suggesting that intact synaptobrevin or synaptobrevin-like
molecules are required for exocytosis. Ultrastructural autoradiography and immunolabel indicate that NT-3 is packaged in
presumptive large dense-core vesicles. These data show that release of
NT-3 from axon terminals depends on multiple regulatory proteins and
ions, including the mobilization of local calcium. The data provide
insight in the mechanisms of anterograde neurotrophins as synaptic modulators.
Key words:
neurotrophic factors; secretion; presynaptic terminals; calcium; axonal transport; neurotrophin; synapse; synaptic
transmission
Copyright © 2002 Society for Neuroscience 0270-6474/02/223931-15$05.00/0
This article has been cited by other articles:

|
 |

|
 |
 
N. Kuczewski, A. Langlois, H. Fiorentino, S. Bonnet, T. Marissal, D. Diabira, N. Ferrand, C. Porcher, and J.-L. Gaiarsa
Spontaneous glutamatergic activity induces a BDNF-dependent potentiation of GABAergic synapses in the newborn rat hippocampus
J. Physiol.,
November 1, 2008;
586(21):
5119 - 5128.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Kolarow, T. Brigadski, and V. Lessmann
Postsynaptic Secretion of BDNF and NT-3 from Hippocampal Neurons Depends on Calcium Calmodulin Kinase II Signaling and Proceeds via Delayed Fusion Pore Opening
J. Neurosci.,
September 26, 2007;
27(39):
10350 - 10364.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. J. Wirth, S. Patz, and P. Wahle
Transcellular induction of neuropeptide Y expression by NT4 and BDNF
PNAS,
February 22, 2005;
102(8):
3064 - 3069.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Conti, Y. P. Tan, and I. Llano
Action Potential-Evoked and Ryanodine-Sensitive Spontaneous Ca2+ Transients at the Presynaptic Terminal of a Developing CNS Inhibitory Synapse
J. Neurosci.,
August 4, 2004;
24(31):
6946 - 6957.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Sadakata, A. Mizoguchi, Y. Sato, R. Katoh-Semba, M. Fukuda, K. Mikoshiba, and T. Furuichi
The Secretory Granule-Associated Protein CAPS2 Regulates Neurotrophin Release and Cell Survival
J. Neurosci.,
January 7, 2004;
24(1):
43 - 52.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. K. Ali and C. Bergson
Elevated Intracellular Calcium Triggers Recruitment of the Receptor Cross-talk Accessory Protein Calcyon to the Plasma Membrane
J. Biol. Chem.,
December 19, 2003;
278(51):
51654 - 51663.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. P. Hibbert, S. J. Morris, N. G. Seidah, and R. A. Murphy
Neurotrophin-4, Alone or Heterodimerized with Brain-derived Neurotrophic Factor, Is Sorted to the Constitutive Secretory Pathway
J. Biol. Chem.,
November 28, 2003;
278(48):
48129 - 48136.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Balkowiec and D. M. Katz
Cellular Mechanisms Regulating Activity-Dependent Release of Native Brain-Derived Neurotrophic Factor from Hippocampal Neurons
J. Neurosci.,
December 1, 2002;
22(23):
10399 - 10407.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|