Ankyrin-G Directly Binds to Kinesin-1 to Transport Voltage-Gated Na+ Channels into Axons

• DOI: 10.1016/j.devcel.2013.11.023
• Publication Date: 2014-01-09T15:45:35Z
• Authors: Joshua Barry; Yuanzheng Gu; Peter Jukkola; Brian O’Neill; Howard Gu; Peter J. Mohler; Keerthi Thirtamar...; Chen Gu
• Keywords: Ankyrin; Ankyrin repeat; NAV1; Kinesin

Action potentials (APs) propagating along axons require the activation of voltage-gated Na+ (Nav) channels. How Nav channels are transported into is unknown. We show that KIF5/kinesin-1 directly binds to ankyrin-G (AnkG) transport axons. KIF5 and Nav1.2 bind multiple sites in AnkG N-terminal domain contains 24 ankyrin repeats. Disrupting AnkG-KIF5 binding with small interfering RNA or dominant-negative constructs markedly reduced channel levels at axon initial segment (AIS) entire axons, thereby decreasing AP firing. Live-cell imaging showed fluorescently tagged cotransported Deleting vivo virus-mediated expression a construct specifically decreased axonal level Nav, but not Kv1.2, mouse cerebellum. These results indicate functions as an adaptor link during before anchoring them AIS nodes Ranvier.