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PMID: 11086001 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

betaIV spectrin, a new spectrin localized at axon initial segments and nodes of ranvier in the central and peripheral nervous system.

The Journal of cell biology ·Vol. 151 ·No. 5 ·2000-11-27 ·Pages 985-1002

Berghs S, Aggujaro D, Dirkx R, Maksimova E, Stabach P, Hermel JM, Zhang JP, Philbrick W, Slepnev V, Ort T, Solimena M

Abstract

We report the identification of betaIV spectrin, a novel spectrin isolated as an interactor of the receptor tyrosine phosphatase-like protein ICA512. The betaIV spectrin gene is located on human and mouse chromosomes 19q13.13 and 7b2, respectively. Alternative splicing of betaIV spectrin generates at least four distinct isoforms, numbered betaIVSigma1-betaIVSigma4 spectrin. The longest isoform (betaIVSigma1 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. betaIVSigma2 and betaIVSigma3 spectrin encompass the NH(2)- and COOH-terminal halves of betaIVSigma1 spectrin, respectively, while betaIVSigma4 spectrin lacks the ERQES and the pleckstrin homology domain. Northern blots revealed an abundant expression of betaIV spectrin transcripts in brain and pancreatic islets. By immunoblotting, betaIVSigma1 spectrin is recognized as a protein of 250 kD. Anti-betaIV spectrin antibodies also react with two additional isoforms of 160 and 140 kD. These isoforms differ from betaIVSigma1 spectrin in terms of their distribution on subcellular fractionation, detergent extractability, and phosphorylation. In islets, the immunoreactivity for betaIV spectrin is more prominent in alpha than in beta cells. In brain, betaIV spectrin is enriched in myelinated neurons, where it colocalizes with ankyrin(G) 480/270-kD at axon initial segments and nodes of Ranvier. Likewise, betaIV spectrin is concentrated at the nodes of Ranvier in the rat sciatic nerve. In the rat hippocampus, betaIVSigma1 spectrin is detectable from embryonic day 19, concomitantly with the appearance of immunoreactivity at the initial segments. Thus, we suggest that betaIVSigma1 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.

MeSH Terms
Amino Acid Sequence Animals Ankyrins/metabolism Autoantigens Axons/chemistry,physiology Blood Proteins/chemistry,genetics Brain Chemistry/physiology COS Cells Chromosomes Cloning, Molecular Cytoplasm/chemistry,metabolism Cytoskeleton/chemistry,metabolism Diabetic Neuropathies/physiopathology Gene Expression/physiology Hippocampus/chemistry,cytology,physiology Humans Islets of Langerhans/chemistry,physiology Male Membrane Proteins/analysis,metabolism Mice Molecular Sequence Data Nerve Tissue Proteins/analysis,chemistry,genetics Phosphoproteins/chemistry,genetics Protein Structure, Tertiary Protein Tyrosine Phosphatases/analysis,metabolism RNA, Messenger/analysis Ranvier's Nodes/chemistry,physiology Rats Rats, Sprague-Dawley Receptor-Like Protein Tyrosine Phosphatases, Class 8 Sciatic Nerve/chemistry,cytology,physiology Signal Transduction/physiology Sodium Channels/metabolism Spectrin/analysis,chemistry,genetics
Chemicals
Ankyrins Autoantigens Blood Proteins Membrane Proteins Nerve Tissue Proteins Phosphoproteins RNA, Messenger Sodium Channels betaIV spectrin platelet protein P47 Spectrin PTPRN protein, human Protein Tyrosine Phosphatases Ptprn protein, mouse Ptprn protein, rat Receptor-Like Protein Tyrosine Phosphatases, Class 8
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Berghs S
Department of Internal Medicine, Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Aggujaro D
Dirkx R
Maksimova E
Stabach P
Hermel J M
Zhang J P
Philbrick W
Slepnev V
Ort T
Solimena M
References (82)
82 references, click to expand
  1. Density of sodium channels in mammalian myelinated nerve fibers and nature of the axonal membrane under the myelin sheath.
    Proc Natl Acad Sci U S A. 1977 Jan;74(1):211-5 PMID: 299947
  2. Identification of a spectrin-like protein in nonerythroid cells.
    Proc Natl Acad Sci U S A. 1981 Dec;78(12):7570-4 PMID: 6950399
  3. F-actin-binding and cross-linking properties of porcine brain fodrin, a spectrin-related molecule.
    J Biol Chem. 1982 Aug 25;257(16):9781-7 PMID: 7107591
  4. Nonerythrocyte spectrins: actin-membrane attachment proteins occurring in many cell types.
    J Cell Biol. 1982 Nov;95(2 Pt 1):478-86 PMID: 6183274
  5. Synapsin I (protein I), a nerve terminal-specific phosphoprotein. I. Its general distribution in synapses of the central and peripheral nervous system demonstrated by immunofluorescence in frozen and plastic sections.
    J Cell Biol. 1983 May;96(5):1337-54 PMID: 6404910
  6. Erythrocyte spectrin is comprised of many homologous triple helical segments.
    Nature. 1984 Sep 13-19;311(5982):177-80 PMID: 6472478
  7. Localization of spectrin in mammalian brain.
    J Neurosci. 1984 Dec;4(12):3089-100 PMID: 6389784
  8. Visualization of the protein associations in the erythrocyte membrane skeleton.
    Proc Natl Acad Sci U S A. 1985 Sep;82(18):6153-7 PMID: 3862123
  9. Plasma membrane structure at the axon hillock, initial segment and cell body of frog dorsal root ganglion cells.
    J Neurocytol. 1985 Oct;14(5):731-47 PMID: 2419519
  10. Brain spectrin(240/235) and brain spectrin(240/235E): two distinct spectrin subtypes with different locations within mammalian neural cells.
    J Cell Biol. 1986 Jun;102(6):2088-97 PMID: 3519621
  11. Spectrin subtypes in mammalian brain: an immunoelectron microscopic study.
    J Neurosci. 1986 Oct;6(10):2977-86 PMID: 3531427
  12. Co-localization of the myelin-associated glycoprotein and the microfilament components, F-actin and spectrin, in Schwann cells of myelinated nerve fibres.
    J Neurocytol. 1989 Feb;18(1):47-60 PMID: 2468742
  13. The 270 kDa splice variant of erythrocyte beta-spectrin (beta I sigma 2) segregates in vivo and in vitro to specific domains of cerebellar neurons.
    J Cell Sci. 1993 Sep;106 ( Pt 1):67-78 PMID: 8270644
  14. The spectrin-based membrane skeleton and micron-scale organization of the plasma membrane.
    Annu Rev Cell Biol. 1993;9:27-66 PMID: 8280463
  15. Identification of two regions of beta G spectrin that bind to distinct sites in brain membranes.
    J Biol Chem. 1994 Feb 11;269(6):4409-16 PMID: 8308011
  16. Islet cell antigen 512 is a diabetes-specific islet autoantigen related to protein tyrosine phosphatases.
    J Immunol. 1994 Mar 15;152(6):3183-8 PMID: 8144912
  17. A partial structural repeat forms the heterodimer self-association site of all beta-spectrins.
    J Biol Chem. 1994 Apr 15;269(15):11400-8 PMID: 8157672
  18. Molecular cloning and identification of a receptor-type protein tyrosine phosphatase, IA-2, from human insulinoma.
    DNA Cell Biol. 1994 May;13(5):505-14 PMID: 8024693
  19. Basic local alignment search tool.
    J Mol Biol. 1990 Oct 5;215(3):403-10 PMID: 2231712
  20. Beta spectrin in human skeletal muscle. Tissue-specific differential processing of 3' beta spectrin pre-mRNA generates a beta spectrin isoform with a unique carboxyl terminus.
    J Biol Chem. 1990 Nov 25;265(33):20449-54 PMID: 2243099
  21. Predicting coiled coils from protein sequences.
    Science. 1991 May 24;252(5009):1162-4 PMID: 2031185
  22. Synapsin I-mediated interaction of brain spectrin with synaptic vesicles.
    J Cell Biol. 1991 Jul;114(2):313-8 PMID: 1906474
  23. Colocalization of synaptophysin with transferrin receptors: implications for synaptic vesicle biogenesis.
    J Cell Biol. 1991 Oct;115(1):151-64 PMID: 1918133
  24. Ankyrin binds to the 15th repetitive unit of erythroid and nonerythroid beta-spectrin.
    J Cell Biol. 1991 Oct;115(1):267-77 PMID: 1833409
  25. Cloning and expression of IDDM-specific human autoantigens.
    Diabetes. 1992 Feb;41(2):183-6 PMID: 1733807
  26. Actin and neurofilament binding domain of brain spectrin beta subunit.
    Eur J Biochem. 1992 Apr 1;205(1):85-91 PMID: 1555607
  27. Characterization of human brain cDNA encoding the general isoform of beta-spectrin.
    J Biol Chem. 1992 Sep 15;267(26):18715-22 PMID: 1527002
  28. Cloning and stable maintenance of 300-kilobase-pair fragments of human DNA in Escherichia coli using an F-factor-based vector.
    Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8794-7 PMID: 1528894
  29. Tyrosine phosphatase activity of lymphoma CD45 (GP180) is regulated by a direct interaction with the cytoskeleton.
    J Biol Chem. 1992 Oct 25;267(30):21551-7 PMID: 1400466
  30. Spectrin redistributes to the cytosol and is phosphorylated during mitosis in cultured cells.
    J Cell Biol. 1992 Dec;119(6):1559-72 PMID: 1469048
  31. Structure, function, and molecular genetics of erythroid membrane skeletal protein 4.1 in normal and abnormal red blood cells.
    Semin Hematol. 1993 Jan;30(1):58-73 PMID: 8434260
  32. Association of GAD-65, but not of GAD-67, with the Golgi complex of transfected Chinese hamster ovary cells mediated by the N-terminal region.
    Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):3073-7 PMID: 8464926
  33. The complete amino acid sequence for brain beta spectrin (beta fodrin): relationship to globin sequences.
    Brain Res Mol Brain Res. 1993 Apr;18(1-2):87-99 PMID: 8479293
  34. Erythroid and nonerythroid spectrins.
    Blood. 1993 Jun 15;81(12):3173-85 PMID: 8507859
  35. Mammalian Ras interacts directly with the serine/threonine kinase Raf.
    Cell. 1993 Jul 16;74(1):205-14 PMID: 8334704
  36. Crystal structure of the repetitive segments of spectrin.
    Science. 1993 Dec 24;262(5142):2027-30 PMID: 8266097
  37. Spectrin (betaSpIIsigma1) is an essential component of synaptic transmission.
    Brain Res. 2000 Jan 3;852(1):161-6 PMID: 10661507
  38. Localization of the tetrodotoxin-resistant sodium channel NaN in nociceptors.
    Neuroreport. 2000 Jan 17;11(1):199-202 PMID: 10683857
  39. Mapping the fodrin binding domain in CD45, a leukocyte membrane-associated tyrosine phosphatase.
    J Biol Chem. 1994 Nov 18;269(46):28576-83 PMID: 7961804
  40. Beta II-spectrin (fodrin) and beta I epsilon 2-spectrin (muscle) contain NH2- and COOH-terminal membrane association domains (MAD1 and MAD2).
    J Biol Chem. 1994 Nov 18;269(46):29212-9 PMID: 7961888
  41. Golgi spectrin: identification of an erythroid beta-spectrin homolog associated with the Golgi complex.
    J Cell Biol. 1994 Nov;127(3):707-23 PMID: 7962054
  42. Drosophila development requires spectrin network formation.
    J Cell Biol. 1995 Jan;128(1-2):71-9 PMID: 7822424
  43. Targeting of the 67-kDa isoform of glutamic acid decarboxylase to intracellular organelles is mediated by its interaction with the NH2-terminal region of the 65-kDa isoform of glutamic acid decarboxylase.
    J Biol Chem. 1995 Feb 3;270(5):2241-6 PMID: 7836456
  44. AnkyrinG. A new ankyrin gene with neural-specific isoforms localized at the axonal initial segment and node of Ranvier.
    J Biol Chem. 1995 Feb 3;270(5):2352-9 PMID: 7836469
  45. Brain spectrin: of mice and men.
    Brain Res Bull. 1995;36(6):593-606 PMID: 7757495
  46. A physical map of chromosome 20 established using fluorescence in situ hybridization and digital image analysis.
    Genomics. 1995 Mar 1;26(1):134-7 PMID: 7782072
  47. Ank3 (epithelial ankyrin), a widely distributed new member of the ankyrin gene family and the major ankyrin in kidney, is expressed in alternatively spliced forms, including forms that lack the repeat domain.
    J Cell Biol. 1995 Jul;130(2):313-30 PMID: 7615634
  48. Structure of the binding site for inositol phosphates in a PH domain.
    EMBO J. 1995 Oct 2;14(19):4676-85 PMID: 7588597
  49. Identification of a second transmembrane protein tyrosine phosphatase, IA-2beta, as an autoantigen in insulin-dependent diabetes mellitus: precursor of the 37-kDa tryptic fragment.
    Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2307-11 PMID: 8637868
  50. ICA 512, an autoantigen of type I diabetes, is an intrinsic membrane protein of neurosecretory granules.
    EMBO J. 1996 May 1;15(9):2102-14 PMID: 8641276
  51. The multidomain protein Trio binds the LAR transmembrane tyrosine phosphatase, contains a protein kinase domain, and has separate rac-specific and rho-specific guanine nucleotide exchange factor domains.
    Proc Natl Acad Sci U S A. 1996 May 28;93(11):5466-71 PMID: 8643598
  52. Molecular cloning of phogrin, a protein-tyrosine phosphatase homologue localized to insulin secretory granule membranes.
    J Biol Chem. 1996 Jul 26;271(30):18161-70 PMID: 8663434
  53. Spectrin: on the path from structure to function.
    Curr Opin Cell Biol. 1996 Feb;8(1):49-55 PMID: 8791400
  54. Substitution of two variant residues in the protein tyrosine phosphatase-like PTP35/IA-2 sequence reconstitutes catalytic activity.
    Biochem Biophys Res Commun. 1996 Oct 14;227(2):581-8 PMID: 8878556
  55. Molecular composition of the node of Ranvier: identification of ankyrin-binding cell adhesion molecules neurofascin (mucin+/third FNIII domain-) and NrCAM at nodal axon segments.
    J Cell Biol. 1996 Dec;135(5):1355-67 PMID: 8947556
  56. Isoforms of ankyrin-3 that lack the NH2-terminal repeats associate with mouse macrophage lysosomes.
    J Cell Biol. 1997 Mar 10;136(5):1059-70 PMID: 9060470
  57. Amphiphysin II (SH3P9; BIN1), a member of the amphiphysin/Rvs family, is concentrated in the cortical cytomatrix of axon initial segments and nodes of ranvier in brain and around T tubules in skeletal muscle.
    J Cell Biol. 1997 Jun 16;137(6):1355-67 PMID: 9182667
  58. Morphogenesis of the node of Ranvier: co-clusters of ankyrin and ankyrin-binding integral proteins define early developmental intermediates.
    J Neurosci. 1997 Sep 15;17(18):7025-36 PMID: 9278538
  59. Evolution of the spectrin repeat.
    Bioessays. 1997 Sep;19(9):811-7 PMID: 9297972
  60. Na,K-ATPase transport from endoplasmic reticulum to Golgi requires the Golgi spectrin-ankyrin G119 skeleton in Madin Darby canine kidney cells.
    Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10711-6 PMID: 9380700
  61. Stabilization of the receptor protein tyrosine phosphatase-like protein ICA512 in GH4C1 cells upon treatment with estradiol, insulin, and epidermal growth factor.
    Endocrinology. 1998 Jun;139(6):2727-33 PMID: 9607778
  62. ADP ribosylation factor regulates spectrin binding to the Golgi complex.
    Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8607-12 PMID: 9671725
  63. Characterization of a new beta-spectrin gene which is predominantly expressed in brain.
    Brain Res Mol Brain Res. 1998 Jun 15;57(2):181-92 PMID: 9675416
  64. A spectrin membrane skeleton of the Golgi complex.
    Biochim Biophys Acta. 1998 Aug 14;1404(1-2):153-60 PMID: 9714784
  65. The role of ankyrin and spectrin in membrane transport and domain formation.
    Curr Opin Cell Biol. 1998 Aug;10(4):542-9 PMID: 9719877
  66. Stromal cells are critical targets in the regulation of mammary ductal morphogenesis by parathyroid hormone-related protein.
    Dev Biol. 1998 Nov 1;203(1):75-89 PMID: 9806774
  67. Vesicular autoantigens of type 1 diabetes.
    Diabetes Metab Rev. 1998 Sep;14(3):227-40 PMID: 9816471
  68. Structural comparisons of calponin homology domains: implications for actin binding.
    Structure. 1998 Nov 15;6(11):1419-31 PMID: 9817844
  69. A widely expressed betaIII spectrin associated with Golgi and cytoplasmic vesicles.
    Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14158-63 PMID: 9826670
  70. AnkyrinG is required for clustering of voltage-gated Na channels at axon initial segments and for normal action potential firing.
    J Cell Biol. 1998 Nov 30;143(5):1295-304 PMID: 9832557
  71. A diffusion barrier maintains distribution of membrane proteins in polarized neurons.
    Nature. 1999 Feb 25;397(6721):698-701 PMID: 10067893
  72. Hematologically important mutations: spectrin and ankyrin variants in hereditary spherocytosis.
    Blood Cells Mol Dis. 1998 Dec;24(4):539-43 PMID: 9887280
  73. Pleckstrin homology domains interact with filamentous actin.
    J Biol Chem. 1999 Jul 9;274(28):19752-61 PMID: 10391917
  74. Post-translational modifications of ICA512, a receptor tyrosine phosphatase-like protein of secretory granules.
    Eur J Neurosci. 1999 Aug;11(8):2609-20 PMID: 10457160
  75. An isoform of ankyrin is localized at nodes of Ranvier in myelinated axons of central and peripheral nerves.
    J Cell Biol. 1990 Apr;110(4):1341-52 PMID: 2139035
  76. Full-length sequence of the cDNA for human erythroid beta-spectrin.
    J Biol Chem. 1990 Jul 15;265(20):11827-32 PMID: 2195026
  77. The identification and sequence of the actin-binding domain of human red blood cell beta-spectrin.
    J Biol Chem. 1990 Jul 15;265(20):11833-40 PMID: 2365703
  78. A beta-spectrin isoform from Drosophila (beta H) is similar in size to vertebrate dystrophin.
    J Cell Biol. 1990 Nov;111(5 Pt 1):1849-58 PMID: 2229176
  79. Identification of a novel C-terminal variant of beta II spectrin: two isoforms of beta II spectrin have distinct intracellular locations and activities.
    J Cell Sci. 2000 Jun;113 ( Pt 11):2023-34 PMID: 10806113
  80. Identification and characterization of beta V spectrin, a mammalian ortholog of Drosophila beta H spectrin.
    J Biol Chem. 2000 Jul 14;275(28):21385-95 PMID: 10764729
  81. The receptor tyrosine phosphatase-like protein ICA512 binds the PDZ domains of beta2-syntrophin and nNOS in pancreatic beta-cells.
    Eur J Cell Biol. 2000 Sep;79(9):621-30 PMID: 11043403
  82. Selective solubilization of a protein component of the red cell membrane.
    Science. 1968 Jan 12;159(3811):203-4 PMID: 5634911
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.151.5.985
Published
2000-11-27
Pages
985-1002
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2174349
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.151.5.985 PMC Full Text View journal details
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