MOLECULAR ANALYSIS OF NERVE TERMINAL DIFFERENTIATION

Project: Research project

Description

The goal of the proposed experiments is to understand, at a molecular level
the role of the target muscle in promoting differentiation of the
presynaptic neuron. Motor neurons in culture with muscle grow and contact
the muscle, synthesize synapse-specific proteins, and concentrate these
proteins at sites of nerve-muscle contact, mimicking processes that occur
during embryonic development. A quantitative assay for the synaptic vesicl
protein p65 will be developed, and used to test effects of muscle on the
regulation of specific protein synthesis. Second, specific antibodies to
cell adhesion molecules and extracellular matrix protein receptors will be
used to test the role of these proteins in triggering synaptic
differentiation. Third, monoclonal antibodies will be raised that recogniz
embryonic or denervated but not adult innervated muscle, to find novel
molecules that may be involved in synaptogenesis. Finally, the
intracellular events involved in presynaptic differentiation will be
examined by focusing on perturbations in common intracellular "second
messengers." An understanding of the molecules and processes involved in
the normal differentiation of synapses is important in order to understand
how these processes go awry in disease states. Besides being directly
valuable for understanding motor neuron trophic disorders (such as
amyotrophic lateral sclerosis) and neuromuscular diseases (such as Eaton-
Lambert syndrome), the information obtained will bear in general on
developmental disorders of the brain and spinal cord.
StatusFinished
Effective start/end date5/10/904/30/95

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $100,326.00
  • National Institutes of Health: $108,371.00

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Muscles
Motor Neurons
Synapses
Lambert-Eaton Myasthenic Syndrome
Neuromuscular Diseases
Motor Neuron Disease
Proteins
Spinal Cord Diseases
Extracellular Matrix Proteins
Embryonic Development
Monoclonal Antibodies
Neurons
Antibodies

ASJC

  • Medicine(all)