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Science 4 February 2000:
Vol. 287. no. 5454, pp. 864 - 869
DOI: 10.1126/science.287.5454.864
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Reports

Synaptic Assembly of the Brain in the Absence of Neurotransmitter Secretion

Matthijs Verhage, 12* Ascanio S. Maia, 1 Jaap J. Plomp, 3 Arjen B. Brussaard, 4 Joost H. Heeroma, 1 Hendrika Vermeer, 1 Ruud F. Toonen, 1 Robert E. Hammer, 5 Timo K. van den Berg, 6 Markus Missler, 2dagger Hans J. Geuze, 7 Thomas C. Südhof 2*

Brain function requires precisely orchestrated connectivity between neurons. Establishment of these connections is believed to require signals secreted from outgrowing axons, followed by synapse formation between selected neurons. Deletion of a single protein, Munc18-1, in mice leads to a complete loss of neurotransmitter secretion from synaptic vesicles throughout development. However, this does not prevent normal brain assembly, including formation of layered structures, fiber pathways, and morphologically defined synapses. After assembly is completed, neurons undergo apoptosis, leading to widespread neurodegeneration. Thus, synaptic connectivity does not depend on neurotransmitter secretion, but its maintenance does. Neurotransmitter secretion probably functions to validate already established synaptic connections.

1 Molecular Neuroscience, Rudolf Magnus Institute, University of Utrecht Medical Centre, Utrecht, Netherlands.
2 Center for Basic Neuroscience, Howard Hughes Medical Institute, and Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
3 Departments of Neurology and Physiology, Leiden University Medical Centre, Leiden, Netherlands.
4 Department of Neurophysiology, Institute for Neurosciences, Vrije Universiteit Amsterdam, Netherlands.
5 Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
6 Department of Cell Biology and Immunology, Vrije Universiteit Amsterdam, Netherlands.
7 Department of Cell Biology, University of Utrecht, Utrecht, Netherlands.
*   To whom correspondence should be addressed. E-mail: m.verhage{at}med.uu.nl (M.V.); tsudho{at}mednet.swmed.edu (T.C.S.)

dagger    Present address: Center for Physiology and Pathophysiology, University of Göttingen, Germany.

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From The Cover: The gene for soluble N-ethylmaleimide sensitive factor attachment protein {alpha} is mutated in hydrocephaly with hop gait (hyh) mice.
H.-K. Hong, A. Chakravarti, and J. S. Takahashi (2004)
PNAS 101, 1748-1753
   Abstract »    Full Text »    PDF »
Miniature synaptic transmission and BDNF modulate dendritic spine growth and form in rat CA1 neurones.
W. J Tyler and L. Pozzo-Miller (2003)
J. Physiol. 553, 497-509
   Abstract »    Full Text »    PDF »
Synaptogenesis in the CNS: An Odyssey from Wiring Together to Firing Together.
D. W Munno and N. I Syed (2003)
J. Physiol. 552, 1-11
   Abstract »    Full Text »    PDF »
Cross Talk between Tetanus Neurotoxin-insensitive Vesicle-associated Membrane Protein-mediated Transport and L1-mediated Adhesion.
P. Alberts, R. Rudge, I. Hinners, A. Muzerelle, S. Martinez-Arca, T. Irinopoulou, V. Marthiens, S. Tooze, F. Rathjen, P. Gaspar, et al. (2003)
Mol. Biol. Cell 14, 4207-4220
   Abstract »    Full Text »    PDF »
Controversies in synaptic vesicle exocytosis.
R. M. Weimer and E. M. Jorgensen (2003)
J. Cell Sci. 116, 3661-3666
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Morphogenesis of the telencephalic commissure requires scaffold protein JNK-interacting protein 3 (JIP3).
N. Kelkar, M.-H. Delmotte, C. R. Weston, T. Barrett, B. J. Sheppard, R. A. Flavell, and R. J. Davis (2003)
PNAS 100, 9843-9848
   Abstract »    Full Text »    PDF »
Insulin Resistance in Tetracycline-Repressible Munc18c Transgenic Mice.
B. A. Spurlin, R. M. Thomas, A. K. Nevins, H.-J. Kim, Y.-J. Kim, H.-L. Noh, G. I. Shulman, J. K. Kim, and D. C. Thurmond (2003)
Diabetes 52, 1910-1917
   Abstract »    Full Text »    PDF »
Developmental Coordination Disorder.
R. C Barnhart, M. J. Davenport, S. B Epps, and V. M Nordquist (2003)
Physical Therapy 83, 722-731
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Phosphorylation of the Autoinhibitory Domain of the Sso t-SNAREs Promotes Binding of the Vsm1 SNARE Regulator in Yeast.
M. Marash and J. E. Gerst (2003)
Mol. Biol. Cell 14, 3114-3125
   Abstract »    Full Text »    PDF »
Ca2+-dependent Phosphorylation of Syntaxin-1A by the Death-associated Protein (DAP) Kinase Regulates Its Interaction with Munc18.
J.-H. Tian, S. Das, and Z.-H. Sheng (2003)
J. Biol. Chem. 278, 26265-26274
   Abstract »    Full Text »    PDF »


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