AnkyrinG Is Required for Clustering of Voltage-gated Na Channels at Axon Initial Segments and for Normal Action Potential Firing Export

@article{citeulike:1692992, abstract = {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. Key words: ankyrinG; sodium channel; neurofascin; clustering; action potential 10.1083/jcb.143.5.1295}, address = {Howard Hughes Medical Institute and Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.}, author = {Zhou, Daixing and Lambert, Stephen and Malen, Peter L. and Carpenter, Scott and Boland, Linda M. and Bennett, Vann}, citeulike-article-id = {1692992}, citeulike-linkout-0 = {http://dx.doi.org/10.1083/jcb.143.5.1295}, citeulike-linkout-1 = {http://jcb.rupress.org/cgi/content/abstract/143/5/1295}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/9832557}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=9832557}, day = {30}, doi = {10.1083/jcb.143.5.1295}, issn = {0021-9525}, journal = {J. Cell Biol.}, month = {November}, number = {5}, pages = {1295--1304}, posted-at = {2007-09-25 14:36:49}, priority = {0}, title = {AnkyrinG Is Required for Clustering of Voltage-gated Na Channels at Axon Initial Segments and for Normal Action Potential Firing}, url = {http://dx.doi.org/10.1083/jcb.143.5.1295}, volume = {143}, year = {1998} }

TY - JOUR ID - citeulike:1692992 L3 - citeulike-article-id:1692992 N2 - 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. Key words: ankyrinG; sodium channel; neurofascin; clustering; action potential 10.1083/jcb.143.5.1295 IS - 5 JF - J. Cell Biol. SN - 0021-9525 AD - Howard Hughes Medical Institute and Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA. EP - 1304 TI - AnkyrinG Is Required for Clustering of Voltage-gated Na Channels at Axon Initial Segments and for Normal Action Potential Firing VL - 143 SP - 1295 AU - Zhou, Daixing AU - Lambert, Stephen AU - Malen, Peter AU - Carpenter, Scott AU - Boland, Linda AU - Bennett, Vann PY - 1998/11/30/ UR - http://dx.doi.org/10.1083/jcb.143.5.1295 ER -