A Cascade Approach to Synapse Formation Based on Thrombogenic and Fibrinolytic Models

  • Barry W. Festoff
  • Jasti S. Rao
  • Bokka R. Reddy
  • Daniel Hantaï
Part of the NATO ASI Series book series (NSSA, volume 191)


Cell-cell interaction in the nervous system has been most intensively studied at the peripheral cholinergic synapse, the neuromuscular junction. The interaction of the motor neuron’s pre-synaptic axonal twigs with the sub-synaptic portion of the muscle fiber surface is influenced both by humoral factors as well as by specific adhesive components of the extracellular matrix (ECM). Neuromuscular synapse formation is initiated with the outgrowth of a neurite destined to be the axon of the motor neuron. This initial ramification begins a complex cascade of steps which include the directed extension of this axonal process through an inhospitable extracellular milieu, the recognition of an appropriate site(s) on the muscle fiber’s surface, the localized deposit, removal and subsequent re-deposition of components of the muscle fiber’s ECM. Eventually, in the neonatal period, a stabilization or linkage of macromolecules of the motor neuron and muscle fiber with the synaptic ECM occurs, which may allow for plasticity or remodelling over the life of the organism. The very nature of these cascade events suggests the well-studied biochemical events associated with regulated extracellular proteolysis underlying thrombogenesis and fibrinolysis. Our laboratory has been actively testing the hypothesis that synapse formation, more specifically neuromuscular junction formation, may be based on molecular mechanisms similar to clot formation and retraction. This MARAIEA CONFERENCE has resulted from theoretical and empirical observations involving several members of the fibrinolytic cascade in muscle and neural cells in culture and in vivo. Some of this information has been presented elsewhere in this volume (see Hantai et al.). In this paper we present evidence for the presence, and probable involvement, of a serine protease inhibitor with anti-thrombin and anti-plasminogen activator (PA) activity in one or more steps that might lead to stabilization of mature neuromuscular synapses.


Amyotrophic Lateral Sclerosis Plasminogen Activator Neurite Outgrowth Neuromuscular Junction Synapse Formation 


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Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Barry W. Festoff
    • 1
    • 2
  • Jasti S. Rao
    • 1
    • 2
  • Bokka R. Reddy
    • 1
    • 2
  • Daniel Hantaï
    • 1
    • 2
  1. 1.Neurobiology Research Laboratory (151)Department of Veterans Affairs Medical CenterKansas CityUSA
  2. 2.Unité 153, I.N.S.E.R.M.ParisFrance

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