biostudies-literatureGu CNINDS NIH HHSPHS HHS25835-47https://www.ebi.ac.uk/biostudies/studies/S-EPMC3138291biostudies-literatureUnknown286(29)Precise localization of axonal ion channels is crucial for proper electrical and chemical functions of axons. In myelinated axons, Kv1 (Shaker) voltage-gated potassium (Kv) channels are clustered in the juxtaparanodal regions flanking the node of Ranvier. The clustering can be disrupted by deletion of various proteins in mice, including contactin-associated protein-like 2 (Caspr2) and transient axonal glycoprotein-1 (TAG-1), a glycosylphosphatidylinositol-anchored cell adhesion molecule. However, the mechanism and function of Kv1 juxtaparanodal clustering remain unclear. Here, using a new myelin coculture of hippocampal neurons and oligodendrocytes, we report that tyrosine phosphorylation plays a critical role in TAG-1-mediated clustering of axonal Kv1.2 channels. In the coculture, myelin The Journal of biological chemistryClustering and activity tuning of Kv1 channels in myelinated hippocampal axons.PMC3138291TA3012A1R01 NS062720R01NS062720Gu CGu YfalseClustering and activity tuning of Kv1 channels in myelinated hippocampal axons.Precise localization of axonal ion channels is crucial for proper electrical and chemical functions of axons. In myelinated axons, Kv1 (Shaker) voltage-gated potassium (Kv) channels are clustered in the juxtaparanodal regions flanking the node of Ranvier. The clustering can be disrupted by deletion of various proteins in mice, including contactin-associated protein-like 2 (Caspr2) and transient axonal glycoprotein-1 (TAG-1), a glycosylphosphatidylinositol-anchored cell adhesion molecule. However, the mechanism and function of Kv1 juxtaparanodal clustering remain unclear. Here, using a new myelin coculture of hippocampal neurons and oligodendrocytes, we report that tyrosine phosphorylation plays a critical role in TAG-1-mediated clustering of axonal Kv1.2 channels. In the coculture, myelin 2011-01-01T00:00:00Z2011 Jul2025-04-05T10:03:08.583Z2019-03-27T03:07:10ZS-EPMC31382912160227810.1074/jbc.M111.21911310.1074/jbc.m111.219113