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FGF14 regulates presynaptic Ca2+ channels and synaptic transmission
Haidun Yan1, Juan L Pablo, Geoffrey S Pitt
1Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Cell Reports
|July 9, 2013
Summary
Fibroblast growth factor homologous factors (FHFs) regulate neuronal ion channels. Mutations in FGF14, linked to spinocerebellar ataxia 27 (SCA27), disrupt Ca2+ channel function, impacting synaptic transmission.
Area of Science:
- Neuroscience
- Molecular Biology
- Channelopathies
Background:
- Fibroblast growth factor homologous factors (FHFs) bind voltage-gated Na+ channels (NaV) and modulate their function.
- Mutations in FGF14 cause spinocerebellar ataxia 27 (SCA27), with presumed dominant-negative effects on NaV currents in cerebellar granule cells.
Purpose of the Study:
- To investigate the role of FGF14 in regulating presynaptic Ca2+ channels.
- To determine the impact of FGF14 knockdown and SCA27 mutations on synaptic function.
Main Methods:
- Knockdown of FGF14 in cerebellar granule cells.
- Measurement of Ca2+ currents and vesicular recycling.
- Electrophysiological recordings of excitatory postsynaptic currents (EPSCs).
Main Results:
- FGF14 knockdown reduced Ca2+ currents and vesicular recycling in granule cells.
- This led to diminished EPSCs at the granule cell to Purkinje cell synapse.
- The SCA27-associated FGF14 mutant caused dominant-negative reductions in Ca2+ currents, vesicular recycling, and EPSCs.
Conclusions:
- FHFs are multimodal regulators of neuronal ion channel function, impacting both NaV and CaV channels.
- Dysregulation of Ca2+ channel function by FGF14 mutations contributes to spinocerebellar ataxia 27 (SCA27).
- FGF14 plays a critical role in presynaptic calcium influx and synaptic transmission.
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