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DPP6 Localization in Brain Supports Function as a Kv4 Channel Associated Protein
Brian D Clark1, Elaine Kwon, Jon Maffie
1Smilow Neuroscience Program, Department of Physiology & Neuroscience New York, USA.
Frontiers in Molecular Neuroscience
|November 4, 2008
Summary
Dipeptidyl peptidase-like protein 6 (DPP6) likely functions as a Kv4 channel subunit in brain neurons, regulating ion currents. DPP6 also shows expression in axons, suggesting additional neural functions beyond Kv4 channel association.
Area of Science:
- Neuroscience
- Molecular Biology
- Ion Channel Physiology
Background:
- The dipeptidyl peptidase-like protein 6 (DPP6) gene is linked to human neural diseases, but its function remained unclear.
- DPP6 was proposed as an auxiliary subunit of neuronal Kv4 K(+) channels, critical for somato-dendritic A-type K(+) currents involved in neuronal excitability and plasticity.
Purpose of the Study:
- To investigate the role of DPP6 in the brain and confirm its association with Kv4 channels.
- To determine if DPP6 has functions independent of Kv4 channels in the central nervous system (CNS).
Main Methods:
- Generation of specific antibodies against DPP6 proteins.
- Immunohistochemical analysis of DPP6 and Kv4.2 subunit distribution in the brain.
- Comparison of cellular and subcellular localization patterns.
Main Results:
- DPP6 expression was prominent in neuronal populations co-expressing Kv4.2.
- Both DPP6 and Kv4.2 proteins were enriched in the dendrites of these neurons.
- DPP6 was also intensely localized to hippocampal mossy fiber axons, which do not express Kv4 proteins.
Conclusions:
- The co-localization strongly supports DPP6 as a functional component of Kv4 channels in brain neurons.
- DPP6's presence in Kv4-negative axons suggests it may have additional, independent roles in the CNS.
