Genes encoding the <i>β</i>1 subunit of voltage‐dependent Na<sup>+</sup> channel in rat, mouse and human contain conserved introns

doi:10.1016/0014-5793(95)01400-4

Cited by 19 publications

(3 citation statements)

References 31 publications

(35 reference statements)

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“…For reasons that are not understood, the amino acid sequence of the β1B C-terminal domain is species-specific (Patino et al, 2011). Further species-specific alternative splicing events have been discovered within SCN1B , including splice variants of the zebrafish SCN1B ortholog scn1ba , scn1ba_tv1 , and scn1ba_tv2 (Fein et al, 2007) with altered protein structure, and β1.2 in rat with an altered 3′ untranslated region (Dib-Hajj and Waxman, 1995). The tissue-specific expression profiles of each of the β subunits are subtly different, but clearly overlapping (Table 1).…”

Section: Molecular Diversity and Functional Architecturementioning

confidence: 99%

Na+ Channel ? Subunits: Overachievers of the Ion Channel Family

Brackenbury¹,

Isom²

2011

Front. Pharmacol.

271

327

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Voltage-gated Na+ channels (VGSCs) in mammals contain a pore-forming α subunit and one or more β subunits. There are five mammalian β subunits in total: β1, β1B, β2, β3, and β4, encoded by four genes: SCN1B–SCN4B. With the exception of the SCN1B splice variant, β1B, the β subunits are type I topology transmembrane proteins. In contrast, β1B lacks a transmembrane domain and is a secreted protein. A growing body of work shows that VGSC β subunits are multifunctional. While they do not form the ion channel pore, β subunits alter gating, voltage-dependence, and kinetics of VGSCα subunits and thus regulate cellular excitability in vivo. In addition to their roles in channel modulation, β subunits are members of the immunoglobulin superfamily of cell adhesion molecules and regulate cell adhesion and migration. β subunits are also substrates for sequential proteolytic cleavage by secretases. An example of the multifunctional nature of β subunits is β1, encoded by SCN1B, that plays a critical role in neuronal migration and pathfinding during brain development, and whose function is dependent on Na+ current and γ-secretase activity. Functional deletion of SCN1B results in Dravet Syndrome, a severe and intractable pediatric epileptic encephalopathy. β subunits are emerging as key players in a wide variety of physiopathologies, including epilepsy, cardiac arrhythmia, multiple sclerosis, Huntington’s disease, neuropsychiatric disorders, neuropathic and inflammatory pain, and cancer. β subunits mediate multiple signaling pathways on different timescales, regulating electrical excitability, adhesion, migration, pathfinding, and transcription. Importantly, some β subunit functions may operate independently of α subunits. Thus, β subunits perform critical roles during development and disease. As such, they may prove useful in disease diagnosis and therapy.

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Section: Molecular Diversity and Functional Architecturementioning

confidence: 99%

Na+ Channel ? Subunits: Overachievers of the Ion Channel Family

Brackenbury¹,

Isom²

2011

Front. Pharmacol.

271

327

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“…Alternative splicing within exon 5 of the zebrafish SCN1B ortholog scn1ba results in two splice variants, scn1ba_tv1 and scn1ba_tv2 , each with novel C-terminal domains and tissue-specific expression patterns (Fein et al, 2007). In rat, the alternative splice product β1.2 contains a novel 3′ untranslated region generated by retention of intron 5 (Dib-Hajj and Waxman, 1995). Another rat splice variant, β1A, contains a novel transmembrane domain and intracellular C-terminus, encoded by retention of intron 3 (Kazen-Gillespie et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Voltage-gated Na⁺channels: Potential for β subunits as therapeutic targets

Brackenbury

Isom

2008

Expert Opinion on Therapeutic Targets

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Background Voltage gated Na+ channels (VGSCs) contain a pore-forming α subunit and one or more β subunits. VGSCs are involved in a wide variety of pathophysiologies, including epilepsy, cardiac arrhythmia, Multiple Sclerosis, periodic paralysis, migraine, neuropathic and inflammatory pain, Huntington’s disease, and cancer. Increasing evidence implicates the β subunits as key players in these disorders. Objective The purpose of this report is to review the recent literature describing the multifunctional roles of VGSC β subunits in the context of their role(s) in disease. Methods An extensive review of the literature on β subunits was performed. Results/conclusion β subunits are multifunctional. As components of VGSC complexes, β subunits mediate signaling processes regulating electrical excitability, adhesion, migration, pathfinding, and transcription. β subunits may prove useful in disease diagnosis and therapy.

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“…Two intron retention events have been documented in the transcription of mammalian SCN1B genes. The first concerns the retention of intron 5 of rat SCN1B and does not change the coding sequence [30]. The second mechanism involves the retention of intron 3, as reported in both rat and human SCN1B genes [31], [32].…”

Section: Discussionmentioning

confidence: 92%

Intron Retention in mRNA Encoding Ancillary Subunit of Insect Voltage-Gated Sodium Channel Modulates Channel Expression, Gating Regulation and Drug Sensitivity

Bourdin

Moignot²,

Wang³

et al. 2013

PLoS ONE

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Insect voltage-gated sodium (Nav) channels are formed by a well-known pore-forming α-subunit encoded by para-like gene and ancillary subunits related to TipE from the mutation “temperature-induced-paralysis locus E.” The role of these ancillary subunits in the modulation of biophysical and pharmacological properties of Na+ currents are not enough documented. The unique neuronal ancillary subunit TipE-homologous protein 1 of Drosophila melanogaster (DmTEH1) strongly enhances the expression of insect Nav channels when heterologously expressed in Xenopus oocytes. Here we report the cloning and functional expression of two neuronal DmTEH1-homologs of the cockroach, Periplaneta americana, PaTEH1A and PaTEH1B, encoded by a single bicistronic gene. In PaTEH1B, the second exon encoding the last 11-amino-acid residues of PaTEH1A is shifted to 3′UTR by the retention of a 96-bp intron-containing coding-message, thus generating a new C-terminal end. We investigated the gating and pharmacological properties of the Drosophila Nav channel variant (DmNav1-1) co-expressed with DmTEH1, PaTEH1A, PaTEH1B or a truncated mutant PaTEH1Δ(270-280) in Xenopus oocytes. PaTEH1B caused a 2.2-fold current density decrease, concomitant with an equivalent α-subunit incorporation decrease in the plasma membrane, compared to PaTEH1A and PaTEH1Δ(270-280). PaTEH1B positively shifted the voltage-dependences of activation and slow inactivation of DmNav1-1 channels to more positive potentials compared to PaTEH1A, suggesting that the C-terminal end of both proteins may influence the function of the voltage-sensor and the pore of Nav channel. Interestingly, our findings showed that the sensitivity of DmNav1-1 channels to lidocaine and to the pyrazoline-type insecticide metabolite DCJW depends on associated TEH1-like subunits. In conclusion, our work demonstrates for the first time that density, gating and pharmacological properties of Nav channels expressed in Xenopus oocytes can be modulated by an intron retention process in the transcription of the neuronal TEH1-like ancillary subunits of P. americana.

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Genes encoding the β1 subunit of voltage‐dependent Na⁺ channel in rat, mouse and human contain conserved introns

Cited by 19 publications

References 31 publications

Na+ Channel ? Subunits: Overachievers of the Ion Channel Family

Na+ Channel ? Subunits: Overachievers of the Ion Channel Family

Voltage-gated Na⁺channels: Potential for β subunits as therapeutic targets

Intron Retention in mRNA Encoding Ancillary Subunit of Insect Voltage-Gated Sodium Channel Modulates Channel Expression, Gating Regulation and Drug Sensitivity

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Genes encoding the β1 subunit of voltage‐dependent Na+ channel in rat, mouse and human contain conserved introns

Cited by 19 publications

References 31 publications

Na+ Channel ? Subunits: Overachievers of the Ion Channel Family

Na+ Channel ? Subunits: Overachievers of the Ion Channel Family

Voltage-gated Na+channels: Potential for β subunits as therapeutic targets

Intron Retention in mRNA Encoding Ancillary Subunit of Insect Voltage-Gated Sodium Channel Modulates Channel Expression, Gating Regulation and Drug Sensitivity

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Resources

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Genes encoding the β1 subunit of voltage‐dependent Na⁺ channel in rat, mouse and human contain conserved introns

Voltage-gated Na⁺channels: Potential for β subunits as therapeutic targets