The voltage-gated sodium channel Nav1.8 produces a tetrodotoxin-resistant current and plays a key role in nociception. Annexin II/p11 binds to Nav1.8 and facilitates insertion of the channel within the cell membrane. However, the mechanisms responsible for removal of specific channels from the cell membrane have not been studied. We have identified a novel protein, clathrin-associated protein-1A (CAP-1A), which contains distinct domains that bind Nav1.8 and clathrin. CAP-1A is abundantly expressed in DRG neurons and colocalizes with Nav1.8 and can form a multiprotein complex with Nav1.8 and clathrin. Coexpression of CAP-1A and Nav1.8 in DRG neurons reduces Na v1.8 current density by approximately 50% without affecting the endogenous or recombinant tetrodotoxin-sensitive currents. This effect of CAP-1A is blocked by bafilomycin A1 treatment of transfected DRG neurons. CAP-1A thus is the first example of an adapter protein that links clathrin and a sodium channel and may regulate Nav1.8 channel density at the cell surface.
ASJC Scopus subject areas
- Molecular Biology
- Cellular and Molecular Neuroscience
- Cell Biology