Ankyrin G restricts ion channel diffusion at the axonal initial segment before the establishment of the diffusion barrier
J Cell Biol.. 2010 Oct 18; 191:(2): 383-95
DOI: jcb.201003042 [pii]10.1083/jcb.201003042
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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.
DOI: 10.1083/jcb.201003042
PMCID: PMC2958486
PMID: 20956383 [Indexed for MEDLINE]