Alterations in transmission, vesicle dynamics, and transmitter release machinery at NCAM-deficient neuromuscular junctions

Neuron. 2001 Dec 6;32(5):815-28. doi: 10.1016/s0896-6273(01)00521-9.


Although functional neuromuscular junctions (NMJs) form in NCAM-deficient mice, they exhibit multiple alterations in presynaptic organization and function. Profound depression and unusual periodic total transmission failures with repetitive stimulation point to a defect in vesicle mobilization/cycling, and these defects were mimicked in (+/+) NMJs by inhibitors of myosin light chain kinase, known to affect vesicle mobilization. Two separate release mechanisms, utilizing different endocytic machinery and Ca(2+) channels, were shown to coexist in (-/-) terminals, with the mature process targeted to presynaptic membrane opposed to muscle, and an abnormally retained immature process targeted to the remainder of the presynaptic terminal and axon. Thus, NCAM plays a critical and heretofore unsuspected role in the molecular organization of the presynaptic NMJ.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium Channels / genetics
  • Calcium Channels / metabolism
  • Electric Stimulation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neural Cell Adhesion Molecules / deficiency*
  • Neural Cell Adhesion Molecules / genetics*
  • Neural Cell Adhesion Molecules / metabolism
  • Neuromuscular Junction / genetics
  • Neuromuscular Junction / metabolism*
  • Neurotransmitter Agents / genetics
  • Neurotransmitter Agents / metabolism*
  • Presynaptic Terminals / metabolism
  • Synaptic Transmission / genetics*
  • Synaptic Vesicles / genetics
  • Synaptic Vesicles / metabolism*


  • Calcium Channels
  • Neural Cell Adhesion Molecules
  • Neurotransmitter Agents