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

doi:10.1083/jcb.200109026

Published 26 November 2001. doi:10.1083/jcb.200109026

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© The Rockefeller University Press, 0021-9525/2001/11/739 $5.00
The Journal of Cell Biology, Volume 155, Number 5, November 26, 2001 739-746

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

Scott M. Jenkins and Vann Bennett

Howard Hughes Medical Institute and Department of Biochemistry and Department Cell Biology, Duke University Medical Center, Durham, NC 27710

Address correspondence to Scott Jenkins, Box 3892, Duke University Medical Center, Durham, NC 27710. Tel.: (919) 684-3105. Fax: (919) 684-3590. E-mail: s.jenkins{at}cellbio.duke.edu

The axon initial segment is an excitable membrane highly enrichedin voltage-gated sodium channels that integrates neuronal inputsand initiates action potentials. This study identifies Na_v1.6as the voltage-gated sodium channel isoform at mature Purkinjeneuron initial segments and reports an essential role for ankyrin-Gin coordinating the physiological assembly of Na_v1.6, ßIVspectrin, and the L1 cell adhesion molecules (L1 CAMs) neurofascinand NrCAM at initial segments of cerebellar Purkinje neurons.Ankyrin-G and ßIV spectrin appear at axon initialsegments by postnatal day 2, whereas L1 CAMs and Na_v1.6 arenot fully assembled at continuous high density along axon initialsegments until postnatal day 9. L1 CAMs and Na_v1.6 thereforedo not initiate protein assembly at initial segments. ßIVspectrin, Na_v1.6, and L1 CAMs are not clustered in adult Purkinjeneuron initial segments of mice lacking cerebellar ankyrin-G.These results support the conclusion that ankyrin-G coordinatesthe physiological assembly of a protein complex containing transmembraneadhesion molecules, voltage-gated sodium channels, and the spectrinmembrane skeleton at axon initial segments.

Key Words: ßIV spectrin; sodium channel Na_v1.6; neurofascin; NrCAM; axon hillock

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