Ankyrin G restricts ion channel diffusion at the axonal initial segment before the establishment of the diffusion barrier

In mammalian neurons, the precise accumulation of sodium channels at the axonal initial segment (AIS) ensures action potential initiation. This accumulation precedes the immobilization of membrane proteins and lipids by a diffusion barrier at the AIS. Using single-particle tracking, we measured the...

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Bibliographic Details
Published in:The Journal of cell biology 2010-10, Vol.191 (2), p.383-395
Main Authors: Brachet, Anna, Leterrier, Christophe, Irondelle, Marie, Fache, Marie-Pierre, Racine, Victor, Sibarita, Jean-Baptiste, Choquet, Daniel, Dargent, Bénédicte
Format: Article
Language:English
Subjects:
Amino Acid Motifs
Amino Acid Sequence
Animals
Ankyrins
Ankyrins - physiology
Axons
Axons - metabolism
Binding Sites
Casein Kinase II - metabolism
Casein Kinase II - physiology
Cell Line
Cell Membrane - metabolism
Cells
Dendrites
Diffusion coefficient
Fluorescence
Gene expression
Ion channels
Kinases
Life Sciences
Lipids
Membrane proteins
Membranes
Mice
Molecular Sequence Data
Neurobiology
Neurons
Neurons and Cognition
Phosphorylation
Protein Transport
Sequence Alignment
Sodium
Sodium Channels - chemistry
Sodium Channels - metabolism
Trajectories
Vehicles
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Summary:In mammalian neurons, the precise accumulation of sodium channels at the axonal initial segment (AIS) ensures action potential initiation. This accumulation precedes the immobilization of membrane proteins and lipids by a diffusion barrier at the AIS. Using single-particle tracking, we measured the mobility of a chimeric ion channel bearing the ankyrin-binding motif of the Nav1.2 sodium channel. We found that ankyrin G (ankG) limits membrane diffusion of ion channels when coexpressed in neuroblastoma cells. Site-directed mutants with decreased affinity for ankG exhibit increased diffusion speeds. In immature hippocampal neurons, we demonstrated that ion channel immobilization by ankG is regulated by protein kinase CK2 and occurs as soon as ankG accumulates at the AIS of elongating axons. Once the diffusion barrier is formed, ankG is still required to stabilize ion channels. In conclusion, our findings indicate that specific binding to ankG constitutes the initial step for Nav channel immobilization at the AIS membrane and precedes the establishment of the diffusion barrier.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.201003042