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Dev Cell. 2014 Jan 27;28(2):117-31. doi: 10.1016/j.devcel.2013.11.023. Epub 2014 Jan 9.

Ankyrin-G directly binds to kinesin-1 to transport voltage-gated Na+ channels into axons.

Author information

1
Molecular, Cellular and Developmental Biology Graduate Program, The Ohio State University, Columbus, OH 43210, USA.
2
Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA.
3
Biomedical Sciences Graduate Program, The Ohio State University, Columbus, OH 43210, USA.
4
Department of Pharmacology, The Ohio State University, Columbus, OH 43210, USA.
5
Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA; Departments of Internal Medicine and Physiology and Cell Biology, The Ohio State University, Columbus, OH 43210, USA.
6
Molecular, Cellular and Developmental Biology Graduate Program, The Ohio State University, Columbus, OH 43210, USA; Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA; Biomedical Sciences Graduate Program, The Ohio State University, Columbus, OH 43210, USA. Electronic address: gu.49@osu.edu.

Abstract

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

PMID:
24412576
PMCID:
PMC3970081
DOI:
10.1016/j.devcel.2013.11.023
[Indexed for MEDLINE]
Free PMC Article

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