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 voltage-gated sodium channels that integrates neuronal inputs and initiates action potentials. This study identifies Nav1.6 as the voltage-gated sodium channel isoform at mature Purkinje neuron initial segments and reports an essential role for ankyrin-G in coordinating the physiological assembly of Nav1.6, betaIV spectrin, and the L1 cell adhesion molecules (L1 CAMs) neurofascin and NrCAM at initial segments of cerebellar Purkinje neurons. Ankyrin-G and betaIV spectrin appear at axon initial segments by postnatal day 2, whereas L1 CAMs and Nav1.6 are not fully assembled at continuous high density along axon initial segments until postnatal day 9. L1 CAMs and Nav1.6 therefore do not initiate protein assembly at initial segments. betaIV spectrin, Nav1.6, and L1 CAMs are not clustered in adult Purkinje neuron initial segments of mice lacking cerebellar ankyrin-G. These results support the conclusion that ankyrin-G coordinates the physiological assembly of a protein complex containing transmembrane adhesion molecules, voltage-gated sodium channels, and the spectrin membrane skeleton at axon initial segments.
Jenkins
S M
SM
Howard Hughes Medical Institute and Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA. s.jenkins@cellbio.duke.edu
Bennett
V
V
D000818:Animals; D017487:Ankyrins / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology; D003599:Cytoskeleton / Q000378:metabolism*; D015640:Ion Channel Gating; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009414:Nerve Growth Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D011689:Purkinje Cells / Q000166:cytology / Q000502:physiology*; D051381:Rats; D015222:Sodium Channels / Q000378:metabolism*; D013049:Spectrin / Q000378:metabolism*
D017487:Ankyrins; D015815:Cell Adhesion Molecules; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; C504593:Nfasc protein, mouse; C504594:Nfasc protein, rat; D015222:Sodium Channels; C417303:betaIV spectrin; D013049:Spectrin