How to Concentrate Sodium Channels

Abstract

Neurons target and concentrate voltage-dependent sodium channels in microdomains of the axonal membrane. These sodium channels are clustered at the axonal initial segment, where action potentials are generated, and in the nodes of Ranvier of myelinated axons. How are these components selectively sorted to these domains? Garrido et al. show that a 27-amino acid motif contained in one of the intracellular linkers of the pore-forming subunit can target and concentrate the sodium channel within the initial segment of the axon. This peptide motif was sufficient to direct and to concentrate different proteins to the initial segment. In addition, the overexpression of a cytosolic chimeric protein containing the motif disorganized endogenous sodium channels. J. J. Garrido, P. Giraud, E. Carlier, F. Fernandes, A. Moussif, M.-P. Fache, D. Debanne, B. Dargent, A targeting motif involved in sodium channel clustering at the axonal initial segment. Science 300, 2091-2094 (2003). [Abstract] [Full Text]