Ankyrin-G coordinates assembly of the spectrin-based membrane skeleton, voltage-gated sodium channels, and L1 CAMs at Purkinje neuron initial segments

The axon initial segment is an excitable membrane highly enriched in voltag e-gated sodium channels that integrates neuronal inputs and initiates actio n potentials. This study identifies Na(v)1.6 as the voltage-gated sodium ch annel isoform at mature Purkinje neuron initial segments and reports an ess ential role for ankyrin-G in coordinating the physiological assembly of Na( v)1.6, beta IV spectrin, and the Ll cell adhesion molecules (L1 CAMs) neuro fascin and NrCAM at initial segments of cerebellar Purkinje neurons. Ankyri n-G and PIV spectrin appear at axon initial segments by postnatal day 2, wh ereas L1 CAMs and Na(v)1.6 are not fully assembled at continuous high densi ty along axon initial segments until postnatal day 9. L1 CAMs and Na(v)1.6 therefore do not initiate protein assembly at initial segments. beta IV spe ctrin, Na(v)1.6, and L1 CAMs are not clustered in adult Purkinje neuron ini tial segments of mice lacking cerebellar ankyrin-G. These results support t he conclusion that ankyrin-G coordinates the physiological assembly of a pr otein complex containing transmembrane adhesion molecules, voltage-gated so dium channels, and the spectrin membrane skeleton at axon initial segments.