Ca(2+) binding protein frequenin mediates GDNF-induced potentiation of Ca(2+) channels and transmitter release.
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.
Wang
C Y
CY
Laboratory of Cellular and Synaptic Neurophysiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Yang
F
F
He
X
X
Chow
A
A
Du
J
J
Russell
J T
JT
Lu
B
B
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D004594:Electrophysiology; D015870:Gene Expression / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000502:physiology; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D009435:Synaptic Transmission / Q000502:physiology; D014981:Xenopus; D029867:Xenopus Proteins
D000906:Antibodies; D020864:Calcium Channels, N-Type; D002135:Calcium-Binding Proteins; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D029867:Xenopus Proteins; C101464:frequenin calcium sensor proteins; D002118:Calcium