Sodium channel expression and assembly during development of retinal ganglion cells

Wollner, Debra A.; Scheinman, Robert I.; Catterall, William A.

doi:10.1016/0896-6273(88)90171-7

Cited by 59 publications

(32 citation statements)

References 35 publications

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“…Consistent with this possibility, expression of an activated form of Raf-1 (30) in PC12 cells results in sustained activation of MAPK and a minor, though significant, increase in Na ϩ current density, without concomitant increases in ␣-subunit mRNA levels (15). Translational and posttranslational events appear to be developmentally regulated, rate-limiting steps in the expression of ␣ subunits in the brain and retina (66,85), and efficient expression of functional Na ϩ channels appears to require subunit assembly, glycosylation, and phosphorylation (23,67,83; for a review, see reference 5). If activation of the Src family of kinases normally influences one of these events, the loss of this signal may decrease the induction of functional Na ϩ channel expression without affecting the induction of type II ␣-subunit mRNA.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Mutant Platelet-Derived Growth Factor Receptors Expressed in PC12 Cells Identifies Signals Governing Sodium Channel Induction during Neuronal Differentiation

Fanger

Vaillancourt

Heasley

et al. 1997

Molecular and Cellular Biology

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The mechanisms governing neuronal differentiation, including the signals underlying the induction of voltage-dependent sodium (Na ؉ ) channel expression by neurotrophic factors, which occurs independent of Ras activity, are not well understood. Therefore, Na ؉ channel induction was analyzed in sublines of PC12 cells stably expressing platelet-derived growth factor (PDGF) ␤ receptors with mutations that eliminate activation of specific signaling molecules. Mutations eliminating activation of phosphatidylinositol 3-kinase (PI3K), phospholipase C ␥ (PLC ␥ ), the GTPase-activating protein (GAP), and Syp phosphatase failed to diminish the induction of type II Na ؉ channel ␣-subunit mRNA and functional Na ؉ channel expression by PDGF, as determined by RNase protection assays and whole-cell patch clamp recording. However, mutation of juxtamembrane tyrosines that bind members of the Src family of kinases upon receptor activation inhibited the induction of functional Na ؉ channels while leaving the induction of type II ␣-subunit mRNA intact. Mutation of juxtamembrane tyrosines in combination with mutations eliminating activation of PI3K, PLC ␥ , GAP, and Syp abolished the induction of type II ␣-subunit mRNA, suggesting that at least partially redundant signaling mechanisms mediate this induction. The differential effects of the receptor mutations on Na ؉ channel expression did not reflect global changes in receptor signaling capabilities, as in all of the mutant receptors analyzed, the induction of c-fos and transin mRNAs still occurred. The results reveal an important role for the Src family in the induction of Na ؉ channel expression and highlight the multiplicity and combinatorial nature of the signaling mechanisms governing neuronal differentiation.Efforts to understand the mechanisms controlling the development and maintenance of the nervous system have identified a number of growth factors with profound effects on neurons. These factors include the neurotrophin family of growth factors, which promote the survival and differentiation of distinct yet overlapping populations of neurons (for reviews, see references 42, 52, and 70). Of the neurotrophins, nerve growth factor (NGF) is the most extensively characterized and has served as the prototype for understanding their actions (for a review, see reference 45). However, other factors, including epidermal growth factor and fibroblast growth factor, also appear to play important roles in the nervous system (22, 82, 84; for reviews, see references 29 and 74). In addition, plateletderived growth factor (PDGF) is expressed in the nervous system and can enhance neuronal survival, neurite outgrowth, and differentiation (14,55,64,68).The effects of growth factors are often mediated through membrane-spanning receptors that exhibit intrinsic tyrosine kinase activity and undergo ligand-dependent autophosphorylation (for a review, see reference 86). The tyrosine-phosphorylated regions in the cytoplasmic domain of the receptor then serve as binding sites for the Src homology 2 (SH...

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Section: Discussionmentioning

confidence: 99%

Analysis of Mutant Platelet-Derived Growth Factor Receptors Expressed in PC12 Cells Identifies Signals Governing Sodium Channel Induction during Neuronal Differentiation

Fanger

Vaillancourt

Heasley

et al. 1997

Molecular and Cellular Biology

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“…Thus, ␤1 subunits have much more striking functional effects on brain and skeletal muscle Na ϩ channels than on cardiac Na ϩ channels. During development of both rat retinal ganglion cells and rat forebrain neurons in vivo, expression of ␤ subunits and their assembly with ␣ subunits is concurrent with a 5-to 10-fold increase in the number of Na ϩ channels (Wollner et al, 1988;Scheinman et al, 1989;Sutkowski and Catterall, 1990). Thus, expression and assembly of ␤ subunits may be a rate-limiting step in Na ϩ channel expression.…”

Section: Effects Of ␤1 Subunits On Expression Of Cardiac Namentioning

confidence: 99%

Modulation of Cardiac Na+ Channel Expression in Xenopus Oocytes by β1 Subunits

Isom

Westenbroek

et al. 1995

Journal of Biological Chemistry

129

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Voltage-gated Na؉ channels consist of a large ␣ subunit of 260 kDa associated with ␤1 and/or ␤2 subunits of 36 and 33 kDa, respectively. ␣ subunits of rat cardiac Na ؉ channels (rH1) are functional when expressed alone in Xenopus oocytes or mammalian cells. ␤1 subunits are present in the heart, and localization of ␤1 subunit mRNA by in situ hybridization shows expression in the perinuclear cytoplasm of cardiac myocytes. Coexpression of ␤1 subunits with rH1 ␣ subunits in Xenopus oocytes increases Na ؉ currents up to 6-fold in a concentration-dependent manner. However, no effects of ␤1 subunit coexpression on the kinetics or voltage dependence of the rH1 Na ؉ current were detected. Increased expression of Na ؉ currents is not observed when an equivalent mRNA encoding a nonfunctional mutant ␤1 subunit is coexpressed. Our results show that ␤1 subunits are expressed in cardiac muscle cells and that they interact with ␣ subunits to increase the expression of cardiac Na ؉ channels in Xenopus oocytes, suggesting that ␤1 subunits are important determinants of the level of excitability of cardiac myocytes in vivo.

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“…Expression of Na+ channels is strongly regulated during development of central neurons, increasing sharply during the postnatal processes of synapse formation and myelination and reaching a plateau level or declining in the mature animal (Gordon et al, 1987;Wollner et al, 1988;Beckh et al, 1989;Scheinman et al, 1989). The tissue-specific regulation of type II Na+ channel expression depends on negative regulatory elements in 5'-flanking regions that prevent expression of the gene in non-neuronal cells (Maue et al, 1990).…”

Section: Cellular Location Of Increased Na+ Channel Densitymentioning

confidence: 99%

Elevated expression of type II Na+ channels in hypomyelinated axons of shiverer mouse brain

1992

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Type I and type III Na+ channels are localized mainly in neuronal cell bodies in mouse brain. Type II channels are preferentially localized in unmyelinated fiber tracts but are not detectable in normally myelinated fibers. In shiverer mice, which lack compact myelin due to a defect in the myelin basic protein gene, elevated expression of type II Na+ channels was observed in the hypomyelinated axons of large-caliber fiber tracts such as the corpus callosum, internal capsule, fimbria, fornix, corpus medullare of the cerebellum, and nigrostriatal pathway by immunocytochemical analysis with subtype-specific antibodies. No difference was observed in the localization of type I and type III Na+ channels between wild-type and shiverer mice. These findings support the hypothesis that type II Na+ channels are preferentially localized in axons of brain neurons and suggest that their density and localization are regulated by myelination. The selective increase in the number of type II channels in hypomyelinated fiber tracts may contribute to the hyperexcitable phenotype of the shiverer mouse.

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Sodium channel expression and assembly during development of retinal ganglion cells

Cited by 59 publications

References 35 publications

Analysis of Mutant Platelet-Derived Growth Factor Receptors Expressed in PC12 Cells Identifies Signals Governing Sodium Channel Induction during Neuronal Differentiation

Analysis of Mutant Platelet-Derived Growth Factor Receptors Expressed in PC12 Cells Identifies Signals Governing Sodium Channel Induction during Neuronal Differentiation

Modulation of Cardiac Na+ Channel Expression in Xenopus Oocytes by β1 Subunits

Elevated expression of type II Na+ channels in hypomyelinated axons of shiverer mouse brain

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