High impact information on SPTBN4

• Conversely, in ankyrin-G-null neurons, betaIV-spectrin is not localized to these sites [1].
• We have generated mice carrying a null mutation in the betaIV-spectrin gene using gene trapping in embryonic stem cells [1].
• These results indicate that betaIV-spectrin and ankyrin-G mutually stabilize the membrane protein cluster and the linked membrane cytoskeleton at AIS and NR [1].
• Mice homozygous for the mutation exhibit tremors and contraction of hindlimbs. betaIV-spectrin expression is mostly restricted to neurons, where it colocalizes with and binds to ankyrin-G at axon initial segments (AISs) and nodes of Ranvier (NR) [1].
• We report the identification of betaIV spectrin, a novel spectrin isolated as an interactor of the receptor tyrosine phosphatase-like protein ICA512 [2].

Biological context of SPTBN4

• Alternative splicing of betaIV spectrin generates at least four distinct isoforms, numbered betaIVSigma1-betaIVSigma4 spectrin [2].
• The betaIV spectrin gene is located on human and mouse chromosomes 19q13.13 and 7b2, respectively [2].
• In betaIV-spectrin-null neurons, neither ankyrin-G nor voltage-gated sodium channels (VGSC) are correctly clustered at these sites, suggesting that impaired action potential caused by mislocalization of VGSC leads to the phenotype [1].
• Ankyrin-G polypeptides are required for restriction of voltage-gated sodium channels, L1 cell adhesion molecules, and beta IV spectrin to axon initial segments and are believed to couple the Na/K-ATPase to the spectrin-actin network at the lateral membrane in epithelial cells [3].
• Autoimmunity to beta IV spectrin in paraneoplastic lower motor neuron syndrome [4].

Anatomical context of SPTBN4

• 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 [2].
• Northern blots revealed an abundant expression of betaIV spectrin transcripts in brain and pancreatic islets [2].
• Likewise, betaIV spectrin is concentrated at the nodes of Ranvier in the rat sciatic nerve [2].
• betaIV spectrin, a new spectrin localized at axon initial segments and nodes of ranvier in the central and peripheral nervous system [2].
• The identification of betaIV spectrin isoforms and surface nodal antigens as novel autoimmune targets in lower motor neuron syndrome provide new insights into the pathogenesis of this severe neurological disease [4].

Other interactions of SPTBN4

• NF-Fc significantly inhibited nodal clustering of Na(+) channels, ankyrin(G), and betaIV spectrin, and modestly reduced Caspr clustering at paranodal junctions; it did not significantly affect lengths or numbers of myelin-positive segments, axon initial segments, or accumulations of phosphorylated-ERM proteins in Schwann cell nodal microvilli [5].

References