Protein kinase CK2 contributes to the organization of sodium channels in axonal membranes by regulating their interactions with ankyrin G.
In neurons, generation and propagation of action potentials requires the precise accumulation of sodium channels at the axonal initial segment (AIS) and in the nodes of Ranvier through ankyrin G scaffolding. We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. Furthermore, we observed that CK2 is highly enriched at the AIS and the nodes of Ranvier in vivo. An ion channel chimera containing the Na(v)1.2 ankyrin-binding motif perturbed endogenous sodium channel accumulation at the AIS, whereas phosphorylation-deficient chimeras did not. Finally, inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G.
Bréchet
Aline
A
Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 641, Marseille F-13916, France.
Fache
Marie-Pierre
MP
Brachet
Anna
A
Ferracci
Géraldine
G
Baude
Agnés
A
Irondelle
Marie
M
Pereira
Sandrine
S
Leterrier
Christophe
C
Dargent
Bénédicte
B
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D017487:Ankyrins / Q000378:metabolism*; D001369:Axons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D016000:Cluster Analysis; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D015640:Ion Channel Gating / Q000187:drug effects; D008969:Molecular Sequence Data; D010766:Phosphorylation / Q000187:drug effects; D017354:Point Mutation / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011901:Ranvier's Nodes / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D012694:Serine / Q000378:metabolism; D015222:Sodium Channels / Q000737:chemistry / Q000378:metabolism*
D017487:Ankyrins; D047428:Protein Kinase Inhibitors; D015222:Sodium Channels; D018698:Glutamic Acid; D012694:Serine; D047390:Casein Kinase II