Ca(2+) binding protein frequenin mediates GDNF-induced potentiation of Ca(2+) channels and transmitter release

Neuron. 2001 Oct 11;32(1):99-112. doi: 10.1016/s0896-6273(01)00434-2.


Molecular mechanisms underlying long-term neurotrophic regulation of synaptic transmission and plasticity are unknown. We report here that long-term treatment of neuromuscular synapses with glial cell line-derived neurotrophic factor (GDNF) potentiates spontaneous and evoked transmitter release, in ways very similar to presynaptic expression of the Ca(2+) binding protein frequenin. GDNF enhances the expression of frequenin in motoneurons, and inhibition of frequenin expression or activity prevents the synaptic action of GDNF. GDNF also facilitates Ca(2+) influx into the nerve terminals during evoked transmission by enhancing Ca(2+) currents. The effect of GDNF on Ca(2+) currents is blocked by inhibition of frequenin expression, occluded by overexpression of frequenin, and is selective to N-type Ca(2+) channels. These results identify an important molecular target that mediates the long-term, synaptic action of a neurotrophic factor.

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Calcium / metabolism*
  • Calcium Channels, N-Type / metabolism*
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / immunology
  • Calcium-Binding Proteins / metabolism*
  • Cells, Cultured
  • Electrophysiology
  • Gene Expression / physiology
  • Glial Cell Line-Derived Neurotrophic Factor
  • Motor Neurons / cytology
  • Motor Neurons / physiology
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / physiology
  • Nerve Growth Factors*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / immunology
  • Nerve Tissue Proteins / metabolism*
  • Neuronal Calcium-Sensor Proteins
  • Neuropeptides
  • Neurotransmitter Agents / metabolism*
  • Oligonucleotides, Antisense / pharmacology
  • Presynaptic Terminals / metabolism
  • RNA, Messenger / analysis
  • Synaptic Transmission / physiology
  • Xenopus
  • Xenopus Proteins*


  • Antibodies
  • Calcium Channels, N-Type
  • Calcium-Binding Proteins
  • Glial Cell Line-Derived Neurotrophic Factor
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Neuronal Calcium-Sensor Proteins
  • Neuropeptides
  • Neurotransmitter Agents
  • Oligonucleotides, Antisense
  • RNA, Messenger
  • Xenopus Proteins
  • frequenin calcium sensor proteins
  • Calcium