Original Article

ßIV Spectrin, a New Spectrin Localized at Axon Initial Segments and Nodes of Ranvier in the Central and Peripheral Nervous System

Correspondence to: Michele Solimena, Department of Internal Medicine, Section of Endocrinology, Yale University School of Medicine, 330 Cedar Street, New Haven, CT 06520. Tel:(203) 737-1037; Fax: (203) 737-2812

We report the identification of ßIV spectrin, a novel spectrin isolated as an interactor of the receptor tyrosine phosphatase-like protein ICA512. The ßIV spectrin gene is located on human and mouse chromosomes 19q13.13 and 7b2, respectively. Alternative splicing of ßIV spectrin generates at least four distinct isoforms, numbered ßIV1–ßIV4 spectrin. The longest isoform (ßIV1 spectrin) includes an actin-binding domain, followed by 17 spectrin repeats, a specific domain in which the amino acid sequence ERQES is repeated four times, several putative SH3-binding sites and a pleckstrin homology domain. ßIV2 and ßIV3 spectrin encompass the NH₂- and COOH-terminal halves of ßIV1 spectrin, respectively, while ßIV4 spectrin lacks the ERQES and the pleckstrin homology domain. Northern blots revealed an abundant expression of ßIV spectrin transcripts in brain and pancreatic islets. By immunoblotting, ßIV1 spectrin is recognized as a protein of 250 kD. Anti–ßIV spectrin antibodies also react with two additional isoforms of 160 and 140 kD. These isoforms differ from ßIV1 spectrin in terms of their distribution on subcellular fractionation, detergent extractability, and phosphorylation. In islets, the immunoreactivity for ßIV spectrin is more prominent in than in ß cells. In brain, ßIV spectrin is enriched in myelinated neurons, where it colocalizes with ankyrin_G 480/270-kD at axon initial segments and nodes of Ranvier. Likewise, ßIV spectrin is concentrated at the nodes of Ranvier in the rat sciatic nerve. In the rat hippocampus, ßIV1 spectrin is detectable from embryonic day 19, concomitantly with the appearance of immunoreactivity at the initial segments. Thus, we suggest that ßIV1 spectrin interacts with ankyrin_G 480/270-kD and participates in the clustering of voltage-gated Na⁺ channels and cell-adhesion molecules at initial segments and nodes of Ranvier.

Key Words: chromosome 19, diabetes, neuropathies, secretion, signal transduction

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Zonta, B., Tait, S., Melrose, S., Anderson, H., Harroch, S., Higginson, J., Sherman, D. L., Brophy, P. J. (2008). Glial and neuronal isoforms of Neurofascin have distinct roles in the assembly of nodes of Ranvier in the central nervous system. J. Cell Biol. 181: 1169-1177 [Abstract] [Full Text]  
• Martin, P.-M., Carnaud, M., del Cano, G. G., Irondelle, M., Irinopoulou, T., Girault, J.-A., Dargent, B., Goutebroze, L. (2008). Schwannomin-Interacting Protein-1 Isoform IQCJ-SCHIP-1 Is a Late Component of Nodes of Ranvier and Axon Initial Segments. J. Neurosci. 28: 6111-6117 [Abstract] [Full Text]  
• Ogawa, Y., Horresh, I., Trimmer, J. S., Bredt, D. S., Peles, E., Rasband, M. N. (2008). Postsynaptic Density-93 Clusters Kv1 Channels at Axon Initial Segments Independently of Caspr2. J. Neurosci. 28: 5731-5739 [Abstract] [Full Text]  
• Susuki, K., Rasband, M. N. (2008). Spectrin and Ankyrin-Based Cytoskeletons at Polarized Domains in Myelinated Axons. Exp. Biol. Med. 233: 394-400 [Abstract] [Full Text]  
• Dzhashiashvili, Y., Zhang, Y., Galinska, J., Lam, I., Grumet, M., Salzer, J. L. (2007). Nodes of Ranvier and axon initial segments are ankyrin G-dependent domains that assemble by distinct mechanisms. J. Cell Biol. 177: 857-870 [Abstract] [Full Text]  
• Ogiwara, I., Miyamoto, H., Morita, N., Atapour, N., Mazaki, E., Inoue, I., Takeuchi, T., Itohara, S., Yanagawa, Y., Obata, K., Furuichi, T., Hensch, T. K., Yamakawa, K. (2007). Nav1.1 Localizes to Axons of Parvalbumin-Positive Inhibitory Interneurons: A Circuit Basis for Epileptic Seizures in Mice Carrying an Scn1a Gene Mutation. J. Neurosci. 27: 5903-5914 [Abstract] [Full Text]  
• Eshed, Y., Feinberg, K., Carey, D. J., Peles, E. (2007). Secreted gliomedin is a perinodal matrix component of peripheral nerves. J. Cell Biol. 177: 551-562 [Abstract] [Full Text]  
• Susuki, K., Rasband, M. N., Tohyama, K., Koibuchi, K., Okamoto, S., Funakoshi, K., Hirata, K., Baba, H., Yuki, N. (2007). Anti-GM1 Antibodies Cause Complement-Mediated Disruption of Sodium Channel Clusters in Peripheral Motor Nerve Fibers. J. Neurosci. 27: 3956-3967 [Abstract] [Full Text]  
• Uemoto, Y., Suzuki, S.-i., Terada, N., Ohno, N., Ohno, S., Yamanaka, S., Komada, M. (2007). Specific Role of the Truncated betaIV-Spectrin {Sigma}6 in Sodium Channel Clustering at Axon Initial Segments and Nodes of Ranvier. J. Biol. Chem. 282: 6548-6555 [Abstract] [Full Text]  
• Hulsmeier, J., Pielage, J., Rickert, C., Technau, G. M., Klambt, C., Stork, T. (2007). Distinct functions of {alpha}-Spectrin and {beta}-Spectrin during axonal pathfinding. Development 134: 713-722 [Abstract] [Full Text]  
• Yang, Y., Ogawa, Y., Hedstrom, K. L., Rasband, M. N. (2007). {beta}IV spectrin is recruited to axon initial segments and nodes of Ranvier by ankyrinG. J. Cell Biol. 176: 509-519 [Abstract] [Full Text]  
• Boiko, T., Vakulenko, M., Ewers, H., Yap, C. C., Norden, C., Winckler, B. (2007). Ankyrin-Dependent and -Independent Mechanisms Orchestrate Axonal Compartmentalization of L1 Family Members Neurofascin and L1/Neuron-Glia Cell Adhesion Molecule. J. Neurosci. 27: 590-603 [Abstract] [Full Text]  
• Simonovic, M., Zhang, Z., Cianci, C. D., Steitz, T. A., Morrow, J. S. (2006). Structure of the Calmodulin {alpha}II-Spectrin Complex Provides Insight into the Regulation of Cell Plasticity. J. Biol. Chem. 281: 34333-34340 [Abstract] [Full Text]  
• Simons, M., Trajkovic, K. (2006). Neuron-glia communication in the control of oligodendrocyte function and myelin biogenesis. J. Cell Sci. 119: 4381-4389 [Abstract] [Full Text]  
• Ogawa, Y., Schafer, D. P., Horresh, I., Bar, V., Hales, K., Yang, Y., Susuki, K., Peles, E., Stankewich, M. C., Rasband, M. N. (2006). Spectrins and ankyrinB constitute a specialized paranodal cytoskeleton.. J. Neurosci. 26: 5230-5239 [Abstract] [Full Text]  
• Inda, M. C., DeFelipe, J., Munoz, A. (2006). Voltage-gated ion channels in the axon initial segment of human cortical pyramidal cells and their relationship with chandelier cells. Proc. Natl. Acad. Sci. USA 103: 2920-2925 [Abstract] [Full Text]  
• Kubosaki, A., Nakamura, S., Notkins, A. L. (2005). Dense Core Vesicle Proteins IA-2 and IA-2{beta}: Metabolic Alterations in Double Knockout Mice. Diabetes 54: S46-S51 [Abstract] [Full Text]  
• Hossain, W. A., Antic, S. D., Yang, Y., Rasband, M. N., Morest, D. K. (2005). Where Is the Spike Generator of the Cochlear Nerve? Voltage-Gated Sodium Channels in the Mouse Cochlea. J. Neurosci. 25: 6857-6868 [Abstract] [Full Text]  
• Devaux, J. J., Scherer, S. S. (2005). Altered Ion Channels in an Animal Model of Charcot-Marie-Tooth Disease Type IA. J. Neurosci. 25: 1470-1480 [Abstract] [Full Text]  
• Tsuboi, T., McMahon, H. T., Rutter, G. A. (2004). Mechanisms of Dense Core Vesicle Recapture following "Kiss and Run" ("Cavicapture") Exocytosis in Insulin-secreting Cells. J. Biol. Chem. 279: 47115-47124 [Abstract] [Full Text]  
• Corfas, G., Velardez, M. O., Ko, C.-P., Ratner, N., Peles, E. (2004). Mechanisms and Roles of Axon-Schwann Cell Interactions. J. Neurosci. 24: 9250-9260 [Full Text]  
• Lacas-Gervais, S., Guo, J., Strenzke, N., Scarfone, E., Kolpe, M., Jahkel, M., De Camilli, P., Moser, T., Rasband, M. N., Solimena, M. (2004). {beta}IV{Sigma}1 spectrin stabilizes the nodes of Ranvier and axon initial segments. J. Cell Biol. 0: jcb.200408007-8 [Abstract] [Full Text]  
• Yang, Y., Lacas-Gervais, S., Morest, D. K., Solimena, M., Rasband, M. N. (2004). {beta}IV Spectrins Are Essential for Membrane Stability and the Molecular Organization of Nodes of Ranvier. J. Neurosci. 24: 7230-7240 [Abstract] [Full Text]  
• Kizhatil, K., Bennett, V. (2004). Lateral Membrane Biogenesis in Human Bronchial Epithelial Cells Requires 190-kDa Ankyrin-G. J. Biol. Chem. 279: 16706-16714 [Abstract] [Full Text]  
• Cai, T., Fukushige, T., Notkins, A. L., Krause, M. (2004). Insulinoma-Associated Protein IA-2, a Vesicle Transmembrane Protein, Genetically Interacts with UNC-31/CAPS and Affects Neurosecretion in Caenorhabditis elegans. J. Neurosci. 24: 3115-3124 [Abstract] [Full Text]  
• Rios, J. C., Rubin, M., Martin, M. St., Downey, R. T., Einheber, S., Rosenbluth, J., Levinson, S. R., Bhat, M., Salzer, J. L. (2003). Paranodal Interactions Regulate Expression of Sodium Channel Subtypes and Provide a Diffusion Barrier for the Node of Ranvier. J. Neurosci. 23: 7001-7011 [Abstract] [Full Text]  
• Gatto, C. L., Walker, B. J., Lambert, S. (2003). Local ERM activation and dynamic growth cones at Schwann cell tips implicated in efficient formation of nodes of Ranvier. J. Cell Biol. 162: 489-498 [Abstract] [Full Text]  
• Spitzenberger, F., Pietropaolo, S., Verkade, P., Habermann, B., Lacas-Gervais, S., Mziaut, H., Pietropaolo, M., Solimena, M. (2003). Islet Cell Autoantigen of 69 kDa Is an Arfaptin-related Protein Associated with the Golgi Complex of Insulinoma INS-1 Cells. J. Biol. Chem. 278: 26166-26173 [Abstract] [Full Text]  
• Garrido, J. J., Giraud, P., Carlier, E., Fernandes, F., Moussif, A., Fache, M.-P., Debanne, D., Dargent, B. (2003). A Targeting Motif Involved in Sodium Channel Clustering at the Axonal Initial Segment. Science 300: 2091-2094 [Abstract] [Full Text]  
• Bailey, S. J., Stocksley, M. A., Buckel, A., Young, C., Slater, C. R. (2003). Voltage-Gated Sodium Channels and AnkyrinG Occupy a Different Postsynaptic Domain from Acetylcholine Receptors from an Early Stage of Neuromuscular Junction Maturation in Rats. J. Neurosci. 23: 2102-2111 [Abstract] [Full Text]  
• Boiko, T., Van Wart, A., Caldwell, J. H., Levinson, S. R., Trimmer, J. S., Matthews, G. (2003). Functional Specialization of the Axon Initial Segment by Isoform-Specific Sodium Channel Targeting. J. Neurosci. 23: 2306-2313 [Abstract] [Full Text]  
• Nedrelow, J. H., Cianci, C. D., Morrow, J. S. (2003). c-Src Binds alpha II Spectrin's Src Homology 3 (SH3) Domain and Blocks Calpain Susceptibility by Phosphorylating Tyr1176. J. Biol. Chem. 278: 7735-7741 [Abstract] [Full Text]  
• Gross, S., Blanchetot, C., Schepens, J., Albet, S., Lammers, R., den Hertog, J., Hendriks, W. (2002). Multimerization of the Protein-tyrosine Phosphatase (PTP)-like Insulin-dependent Diabetes Mellitus Autoantigens IA-2 and IA-2beta with Receptor PTPs (RPTPs). INHIBITION OF RPTPalpha ENZYMATIC ACTIVITY. J. Biol. Chem. 277: 48139-48145 [Abstract] [Full Text]  
• Rasband, M. N., Park, E. W., Zhen, D., Arbuckle, M. I., Poliak, S., Peles, E., Grant, S. G.N., Trimmer, J. S. (2002). Clustering of neuronal potassium channels is independent of their interaction with PSD-95. J. Cell Biol. 159: 663-672 [Abstract] [Full Text]  
• Derrien, V., Couillault, C., Franco, M., Martineau, S., Montcourrier, P., Houlgatte, R., Chavrier, P. (2002). A conserved C-terminal domain of EFA6-family ARF6-guanine nucleotide exchange factors induces lengthening of microvilli-like membrane protrusions. J. Cell Sci. 115: 2867-2879 [Abstract] [Full Text]  
• Saeki, K., Zhu, M., Kubosaki, A., Xie, J., Lan, M. S., Notkins, A. L. (2002). Targeted Disruption of the Protein Tyrosine Phosphatase-Like Molecule IA-2 Results in Alterations in Glucose Tolerance Tests and Insulin Secretion. Diabetes 51: 1842-1850 [Abstract] [Full Text]  
• Nicolas, G., Fournier, C. M., Galand, C., Malbert-Colas, L., Bournier, O., Kroviarski, Y., Bourgeois, M., Camonis, J. H., Dhermy, D., Grandchamp, B., Lecomte, M.-C. (2002). Tyrosine Phosphorylation Regulates Alpha II Spectrin Cleavage by Calpain. Mol. Cell. Biol. 22: 3527-3536 [Abstract] [Full Text]  
• Bennett, V., Baines, A. J. (2001). Spectrin and Ankyrin-Based Pathways: Metazoan Inventions for Integrating Cells Into Tissues. Physiol. Rev. 81: 1353-1392 [Abstract] [Full Text]  
• Berghs, S., Ferracci, F., Maksimova, E., Gleason, S., Leszczynski, N., Butler, M., De Camilli, P., Solimena, M. (2001). Autoimmunity to beta IV spectrin in paraneoplastic lower motor neuron syndrome. Proc. Natl. Acad. Sci. USA 98: 6945-6950 [Abstract] [Full Text]  
• Tse, W. T., Tang, J., Jin, O., Korsgren, C., John, K. M., Kung, A. L., Gwynn, B., Peters, L. L., Lux, S. E. (2001). A New Spectrin, beta IV, Has a Major Truncated Isoform That Associates with Promyelocytic Leukemia Protein Nuclear Bodies and the Nuclear Matrix. J. Biol. Chem. 276: 23974-23985 [Abstract] [Full Text]  
• Kontrogianni-Konstantopoulos, A., Frye, C. S., Benz, E. J. Jr., Huang, S.-C. (2001). The Prototypical 4.1R-10-kDa Domain and the 4.1G-10-kDa Paralog Mediate Fodrin-Actin Complex Formation. J. Biol. Chem. 276: 20679-20687 [Abstract] [Full Text]  
• Jenkins, S. M., Bennett, V. (2002). Developing nodes of Ranvier are defined by ankyrin-G clustering and are independent of paranodal axoglial adhesion. Proc. Natl. Acad. Sci. USA 99: 2303-2308 [Abstract] [Full Text]  
• Jenkins, S. M., Bennett, V. (2001). Ankyrin-G coordinates assembly of the spectrin-based membrane skeleton, voltage-gated sodium channels, and L1 CAMs at Purkinje neuron initial segments. J. Cell Biol. 155: 739-746 [Abstract] [Full Text]  
• Komada, M., Soriano, P. (2002). {beta}IV-spectrin regulates sodium channel clustering through ankyrin-G at axon initial segments and nodes of Ranvier. J. Cell Biol. 156: 337-348 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents