Gene Symbol: Sptbn4
Description: spectrin beta, non-erythrocytic 4
Alias: 1700022P15Rik, 5830426A08Rik, ROSA62, SpbIV, Spnb4, dyn, lnd, nmf261, nmf379, spectrin beta chain, non-erythrocytic 4, beta-spectrin 4, lumbosacral neuroaxonal dystrophy, neuroaxonal dystrophy, quivering, spectrin beta 4
Species: mouse
Products:     Sptbn4

Top Publications

  1. Horner K, Lenoir M, Bock G. Distortion product otoacoustic emissions in hearing-impaired mutant mice. J Acoust Soc Am. 1985;78:1603-11 pubmed
    ..The quivering mutant has a central auditory dysfunction associated with the nuclei of the superior olivary complex and the ..
  2. Grosson C, Cannon S, Corey D, Gusella J. Sequence of the voltage-gated sodium channel beta1-subunit in wild-type and in quivering mice. Brain Res Mol Brain Res. 1996;42:222-6 pubmed
    ..As Scnlb maps to Chr 7, in close genetic proximity to the quivering gene (qv), the coding region of Scnlb was also cloned from a qvJ/qvJ homozygous mouse and assessed as a ..
  3. Tse W, Tang J, Jin O, Korsgren C, John K, Kung A, et al. 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. 2001;276:23974-85 pubmed
    ..Spectrin betaIV is the first beta-spectrin associated with a subnuclear structure and may be part of a nuclear scaffold to which gene regulatory machinery binds. ..
  4. Uemoto Y, Suzuki S, Terada N, Ohno N, Ohno S, Yamanaka S, et al. Specific role of the truncated betaIV-spectrin Sigma6 in sodium channel clustering at axon initial segments and nodes of ranvier. J Biol Chem. 2007;282:6548-55 pubmed
    ..We conclude that the truncated betaIV-spectrin isoform Sigma6 plays a specific role in clustering voltage-gated sodium channels, whereas it is dispensable for membrane stabilization at axon initial segments and nodes of Ranvier. ..
  5. Lacas Gervais S, Guo J, Strenzke N, Scarfone E, Kolpe M, Jahkel M, et al. BetaIVSigma1 spectrin stabilizes the nodes of Ranvier and axon initial segments. J Cell Biol. 2004;166:983-90 pubmed
    ..These ultrastructural changes can explain the motor and auditory neuropathies present in betaIVSigma1 -/- mice and point to the betaIVSigma1 spectrin isoform as a master-stabilizing factor of AIS/NR membranes. ..
  6. Yang Y, Lacas Gervais S, Morest D, Solimena M, Rasband M. BetaIV spectrins are essential for membrane stability and the molecular organization of nodes of Ranvier. J Neurosci. 2004;24:7230-40 pubmed
    ..To investigate the molecular organization of nodes, we analyzed qv(3J)"quivering" mice, whose betaIV spectrins have a truncated proline-rich "specific" domain (SD) and lack the ..
  7. Berghs S, Aggujaro D, Dirkx R, Maksimova E, Stabach P, Hermel J, et al. betaIV spectrin, a new spectrin localized at axon initial segments and nodes of ranvier in the central and peripheral nervous system. J Cell Biol. 2000;151:985-1002 pubmed
    ..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. ..
  8. Parkinson N, Olsson C, Hallows J, McKee Johnson J, Keogh B, Noben Trauth K, et al. Mutant beta-spectrin 4 causes auditory and motor neuropathies in quivering mice. Nat Genet. 2001;29:61-5 pubmed
    The autosomal recessive mouse mutation quivering (qv), which arose spontaneously in 1953, produces progressive ataxia with hind limb paralysis, deafness and tremor...
  9. Ogawa Y, Schafer D, Horresh I, Bar V, Hales K, Yang Y, et al. Spectrins and ankyrinB constitute a specialized paranodal cytoskeleton. J Neurosci. 2006;26:5230-9 pubmed
    ..Our results demonstrate that the paranodal junction contains specialized cytoskeletal components that may be important to stabilize axon-glia interactions and contribute to the membrane protein diffusion barrier found at paranodes. ..

More Information


  1. Komada M, Soriano P. [Beta]IV-spectrin regulates sodium channel clustering through ankyrin-G at axon initial segments and nodes of Ranvier. J Cell Biol. 2002;156:337-48 pubmed
    ..These results indicate that betaIV-spectrin and ankyrin-G mutually stabilize the membrane protein cluster and the linked membrane cytoskeleton at AIS and NR. ..
  2. Legendre K, Safieddine S, Küssel Andermann P, Petit C, El Amraoui A. alphaII-betaV spectrin bridges the plasma membrane and cortical lattice in the lateral wall of the auditory outer hair cells. J Cell Sci. 2008;121:3347-56 pubmed publisher
    ..We conclude that the cortical network involved in the sound-induced electromotility of OHCs contains alphaII-betaV spectrin, and not the conventional alphaII-betaII spectrin. ..
  3. Yang Y, Ogawa Y, Hedstrom K, Rasband M. betaIV spectrin is recruited to axon initial segments and nodes of Ranvier by ankyrinG. J Cell Biol. 2007;176:509-19 pubmed
    ..Finally, using adenovirus for transgene delivery into myelinated neurons, we demonstrate that betaIV spectrin recruitment to nodes of Ranvier also depends on binding to ankG. ..
  4. van Beuningen S, Will L, Harterink M, Chazeau A, van Battum E, Frias C, et al. TRIM46 Controls Neuronal Polarity and Axon Specification by Driving the Formation of Parallel Microtubule Arrays. Neuron. 2015;88:1208-1226 pubmed publisher
    ..Thus, TRIM46 defines a unique axonal cytoskeletal compartment for regulating microtubule organization during neuronal development. ..
  5. Rogers H, Sheehan K, Brunt L, Dower S, Unanue E, Schreiber R. Interleukin 1 participates in the development of anti-Listeria responses in normal and SCID mice. Proc Natl Acad Sci U S A. 1992;89:1011-5 pubmed
  6. Hund T, Snyder J, Wu X, Glynn P, Koval O, Onal B, et al. ?(IV)-Spectrin regulates TREK-1 membrane targeting in the heart. Cardiovasc Res. 2014;102:166-75 pubmed publisher
    ..These data provide new insight into membrane targeting of TREK-1 in the heart and establish a broader role for ?(IV)-spectrin in organizing functional membrane domains critical for normal heart function. ..
  7. Hossain W, Antic S, Yang Y, Rasband M, Morest D. Where is the spike generator of the cochlear nerve? Voltage-gated sodium channels in the mouse cochlea. J Neurosci. 2005;25:6857-68 pubmed
    ..In the deaf mutant quivering mouse, the localization of Nav1.6 was disrupted in the sensory epithelium and ganglion...
  8. Martin P, Carnaud M, Garcia del Caño G, Irondelle M, Irinopoulou T, Girault J, et al. Schwannomin-interacting protein-1 isoform IQCJ-SCHIP-1 is a late component of nodes of Ranvier and axon initial segments. J Neurosci. 2008;28:6111-7 pubmed publisher
    ..IQCJ-SCHIP-1 was also absent from central NRs and AISs of quivering mice, which have a mutation of betaIV-spectrin...
  9. Glynn P, Musa H, Wu X, Unudurthi S, Little S, Qian L, et al. Voltage-Gated Sodium Channel Phosphorylation at Ser571 Regulates Late Current, Arrhythmia, and Cardiac Function In Vivo. Circulation. 2015;132:567-77 pubmed publisher
    ..Relevant for improved rational design of potential therapies, our findings demonstrate that Ser571-dependent regulation of Nav1.5 specifically tunes INa,L without altering critical physiological components of the current. ..
  10. Maddala R, Skiba N, Lalane R, Sherman D, Brophy P, Rao P. Periaxin is required for hexagonal geometry and membrane organization of mature lens fibers. Dev Biol. 2011;357:179-90 pubmed publisher
    ..Hence, there may be functional parallels between the roles of Prx in membrane stabilization of the myelin sheath and the lens fiber cell. ..
  11. Feinberg K, Eshed Eisenbach Y, Frechter S, Amor V, Salomon D, Sabanay H, et al. A glial signal consisting of gliomedin and NrCAM clusters axonal Na+ channels during the formation of nodes of Ranvier. Neuron. 2010;65:490-502 pubmed publisher
    ..Together, these two cooperating mechanisms ensure fast and efficient conduction in myelinated nerves. ..
  12. Winkels R, Jedlicka P, Weise F, Schultz C, Deller T, Schwarzacher S. Reduced excitability in the dentate gyrus network of betaIV-spectrin mutant mice in vivo. Hippocampus. 2009;19:677-86 pubmed publisher
    ..It provides mechanical support for the axon and anchors membrane proteins. Quivering (qv(3j)) mice lack functional betaIV-spectrin and have reduced voltage-gated sodium channel (VGSC) ..
  13. Susuki K, Chang K, Zollinger D, Liu Y, Ogawa Y, Eshed Eisenbach Y, et al. Three mechanisms assemble central nervous system nodes of Ranvier. Neuron. 2013;78:469-82 pubmed publisher
    ..Our results demonstrate that ECM, paranodal, and axonal cytoskeletal mechanisms ensure robust CNS nodal Na? channel clustering. ..
  14. Sohn P, Tracy T, Son H, Zhou Y, Leite R, Miller B, et al. Acetylated tau destabilizes the cytoskeleton in the axon initial segment and is mislocalized to the somatodendritic compartment. Mol Neurodegener. 2016;11:47 pubmed publisher
    ..Together, these findings demonstrate that tau acetylation contributes to the pathogenesis of neurodegenerative disease by compromising the cytoskeletal sorting machinery in the AIS. ..
  15. Hund T, Koval O, Li J, Wright P, Qian L, Snyder J, et al. A ?(IV)-spectrin/CaMKII signaling complex is essential for membrane excitability in mice. J Clin Invest. 2010;120:3508-19 pubmed publisher
    ..Collectively, our data define an unexpected but indispensable molecular platform that determines membrane excitability in the mouse heart and brain. ..
  16. Martin P, Cifuentes Diaz C, Devaux J, Garcia M, Bureau J, Thomasseau S, et al. Schwannomin-interacting Protein 1 Isoform IQCJ-SCHIP1 Is a Multipartner Ankyrin- and Spectrin-binding Protein Involved in the Organization of Nodes of Ranvier. J Biol Chem. 2017;292:2441-2456 pubmed publisher
    ..Our work reveals that IQCJ-SCHIP1 interacts with several major nodal proteins, and we suggest that it contributes to a higher organizational level of the AnkG/?IV-spectrin network critical for node integrity. ..
  17. Kosaka T, Komada M, Kosaka K. Sodium channel cluster, betaIV-spectrin and ankyrinG positive "hot spots" on dendritic segments of parvalbumin-containing neurons and some other neurons in the mouse and rat main olfactory bulbs. Neurosci Res. 2008;62:176-86 pubmed publisher
    ..Our study suggested that these morphologically identified dendritic "hot spots" might correspond to dendritic spike generation sites of those neurons. ..
  18. Kosaka T, Kosaka K. Heterogeneity of parvalbumin-containing neurons in the mouse main olfactory bulb, with special reference to short-axon cells and betaIV-spectrin positive dendritic segments. Neurosci Res. 2008;60:56-72 pubmed
    ..The present study revealed the diversity of parvalbumin-positive neurons in the mouse MOB and their particular structural properties hitherto unknown. ..
  19. Jones S, Johnson K, Yu H, Erway L, Alagramam K, Pollak N, et al. A quantitative survey of gravity receptor function in mutant mouse strains. J Assoc Res Otolaryngol. 2005;6:297-310 pubmed
    ..Interestingly, some heterozygote groups also showed abnormalities in one or more VsEP response parameters, suggesting that vestibular dysfunction, although less severe, may be present in some heterozygous animals. ..
  20. Yoon C. Electrophoretic analysis of the serum proteins of neurological mutations in mice. Science. 1961;134:1009-10 pubmed
    The serum proteins of three neurological mutations, tremulous, quivering, and waddler, were studied...
  21. Yoon C, Harris S. Cholinesterase studies of neurologic mutants in mice. 1. Alterations in serum cholinesterase levels. Neurology. 1962;12:423-6 pubmed
  22. Zhang A, Desmazieres A, Zonta B, Melrose S, Campbell G, Mahad D, et al. Neurofascin 140 is an embryonic neuronal neurofascin isoform that promotes the assembly of the node of Ranvier. J Neurosci. 2015;35:2246-54 pubmed publisher
    ..This expands the critical role of the Nfasc gene in the function of myelinated axons and reveals further redundancy in the mechanisms required for the formation of this crucial structure in the vertebrate nervous system. ..
  23. Bronson R, Sweet H, Spencer C, Davisson M. Genetic and age related models of neurodegeneration in mice: dystrophic axons. J Neurogenet. 1992;8:71-83 pubmed
    ..The distribution of DA in these mutants is defined by their names, lumbosacral neuroaxonal dystrophy (lnd), located on Chromosome 7, generalized neuroaxonal dystrophy (gnd) and vestibulomotor ..
  24. Nishimura K, Akiyama H, Komada M, Kamiguchi H. betaIV-spectrin forms a diffusion barrier against L1CAM at the axon initial segment. Mol Cell Neurosci. 2007;34:422-30 pubmed
    ..Our results highlight the role of betaIV-spectrin and ankyrinG as critical components of a selective barrier against L1CAM. ..
  25. Devaux J. The C-terminal domain of ßIV-spectrin is crucial for KCNQ2 aggregation and excitability at nodes of Ranvier. J Physiol. 2010;588:4719-30 pubmed publisher
    ..Here, I investigated the physiology of the neuromuscular junction and peripheral nerves in quivering-3J mice, which show a frame-shift base insertion in the Spnb4 gene and lack the C-terminus of ?IV-spectrin...
  26. Xu K, Zhong G, Zhuang X. Actin, spectrin, and associated proteins form a periodic cytoskeletal structure in axons. Science. 2013;339:452-6 pubmed publisher
    ..Sodium channels in axons were distributed in a periodic pattern coordinated with the underlying actin-spectrin-based cytoskeleton. ..
  27. Le Bras B, Fréal A, Czarnecki A, Legendre P, Bullier E, Komada M, et al. In vivo assembly of the axon initial segment in motor neurons. Brain Struct Funct. 2014;219:1433-50 pubmed publisher
    ..5 these nascent AISs are already able to generate spikes. Using knock-out mice, we demonstrated that neither ?4-spectrin nor Neurofascin control the distal-to-proximal restriction of AnkG. ..
  28. Kline C, Wright P, Koval O, Zmuda E, Johnson B, Anderson M, et al. ?IV-Spectrin and CaMKII facilitate Kir6.2 regulation in pancreatic beta cells. Proc Natl Acad Sci U S A. 2013;110:17576-81 pubmed publisher
  29. Horner K, Bock G. Combined electrophysiological and autoradiographic delimitation of retrocochlear dysfunction in a mouse mutant. Brain Res. 1985;331:217-23 pubmed
    The hereditary retrocochlear dysfunction in the quivering (qv) mouse was investigated with autoradiography and single unit recordings...
  30. Litt M, Luty J, Kwak M, Allen L, Magenis R, Mandel G. Localization of a human brain sodium channel gene (SCN2A) to chromosome 2. Genomics. 1989;5:204-8 pubmed
    ..In situ hybridization to metaphase chromosomes confirms this assignment and indicates regional localization to 2q21-q33. The probe also reveals a frequent two-allele HaeIII RFLP. ..