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Voltage-gated sodium channels (NaCh) are colocalized with isoforms of the membrane-skeletal protein ankyrinG at axon initial segments, nodes of Ranvier, and postsynaptic folds of the mammalian neuromuscular junction. The role of ankyrinG in directing NaCh localization to axon initial segments was evaluated by region-specific knockout of ankyrinG in the mouse cerebellum. Mutant mice exhibited a progressive ataxia beginning around postnatal day P16 and subsequent loss of Purkinje neurons. In mutant mouse cerebella, NaCh were absent from axon initial segments of granule cell neurons, and Purkinje cells showed deficiencies in their ability to initiate action potentials and support rapid, repetitive firing. Neurofascin, a member of the L1CAM family of ankyrin-binding cell adhesion molecules, also exhibited impaired localization to initial segments of Purkinje cell neurons. These results demonstrate that ankyrinG is essential for clustering NaCh and neurofascin at axon initial segments and is required for physiological levels of sodium channel activity.
Pubmed ID: 9832557 RIS Download
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Biomedical technology research center that develops new technologies for modeling cell biological processes. The technologies are integrated through Virtual Cell, a problem-solving environment built on a central database and disseminated as a Web application for the analysis, modeling and simulation of cell biological processes. NRCAM resides at the Center for Cell Analysis and Modeling, CCAM, and provides a vast array of laboratory equipment that can be used for obtaining experimental data needed to create and enhance Virtual Cell models. Microscopy instrumentation includes three confocal laser scanning microscopes including UV excitation, nonlinear optical microscopy utilizing a titanium sapphire pulsed laser, confocal-based fluorescence correlation spectroscopy, wide-field imaging workstation with cooled CCD and rapid excitation filter wheel, and dual-wavelength spectrofluorometer. Access to the facilities and technical staff is open to all researchers.
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