Voltage-gated sodium channel organization in neurons: protein interactions and trafficking pathways.
In neurons, voltage-gated sodium (Nav) channels underlie the generation and propagation of the action potential. The proper targeting and concentration of Nav channels at the axon initial segment (AIS) and at the nodes of Ranvier are therefore vital for neuronal function. In AIS and nodes, Nav channels are part of specific supra-molecular complexes that include accessory proteins, adhesion proteins and cytoskeletal adaptors. Multiple approaches, from biochemical characterization of protein-protein interactions to functional studies using mutant mice, have addressed the mechanisms of Nav channel targeting to AIS and nodes. This review summarizes our current knowledge of both the intrinsic determinants and the role of partner proteins in Nav targeting. A few fundamental trafficking mechanisms, such as selective endocytosis and diffusion/retention, have been characterized. However, a lot of exciting questions are still open, such as the mechanism of differentiated Nav subtype localization and targeting, and the possible interplay between electrogenesis properties and Nav concentration at the AIS and the nodes.
Leterrier
Christophe
C
INSERM UMR 641, Marseille F-13916, France.
Brachet
Anna
A
Fache
Marie-Pierre
MP
Dargent
Bénédicte
B
D000818:Animals; D001369:Axons / Q000378:metabolism; D004058:Diffusion; D004705:Endocytosis; D006801:Humans; D015640:Ion Channel Gating; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D025941:Protein Interaction Mapping; D021381:Protein Transport; D011901:Ranvier's Nodes / Q000378:metabolism; D015398:Signal Transduction; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology*
D046912:Multiprotein Complexes; D015222:Sodium Channels