Embryonic and larval expression of zebrafish voltage‐gated sodium channel α‐subunit genes

Novak, Alicia E.; Taylor, Alison D.; Pineda, Ricardo; Lasda, Erika; Wright, Melissa A.; Ribera, Angeles B.

doi:10.1002/dvdy.20811

Cited by 81 publications

(89 citation statements)

References 60 publications

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“…Recordings from several types of excitable cells also established that RNF121 is required for the transport of functional Na V channels to the membrane of these cells. Taken together with the reported spatial expression of Na V orthologs in zebrafish [RBs, Na V 1.1 and Na V 1.6 (11); skeletal muscle, Na V 1.4; motor neurons, Na V 1.5 and Na V 1.6 (20)], RNF121 is at least required for Na V channel complexes composed of these four α-subunits. However, given its ubiquitous expression in larvae (21), RNF121 might contribute to the quality control of all Na V channels.…”

Section: Discussionmentioning

confidence: 59%

RING finger protein 121 facilitates the degradation and membrane localization of voltage-gated sodium channels

Ogino

Low

Yamada

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Following their synthesis in the endoplasmic reticulum (ER), voltagegated sodium channels (Na V ) are transported to the membranes of excitable cells, where they often cluster, such as at the axon initial segment of neurons. Although the mechanisms by which Na V channels form and maintain clusters have been extensively examined, the processes that govern their transport and degradation have received less attention. Our entry into the study of these processes began with the isolation of a new allele of the zebrafish mutant alligator, which we found to be caused by mutations in the gene encoding really interesting new gene (RING) finger protein 121 (RNF121), an E3-ubiquitin ligase present in the ER and cis-Golgi compartments. Here we demonstrate that RNF121 facilitates two opposing fates of Na V channels: (i) ubiquitin-mediated proteasome degradation and (ii) membrane localization when coexpressed with auxiliary Na V β subunits. Collectively, these results indicate that RNF121 participates in the quality control of Na V channels during their synthesis and subsequent transport to the membrane.oltage-gated sodium channels (Na V ) are large (∼230 kDa) multipass transmembrane proteins (1). The Na V channel family is comprised of nine members (Na V 1.1-Na V 1.9), whose activity typically underlies the rising phase of action potentials in excitable cells. In excitable cells, Na V channels form complexes with auxiliary β subunits (Na V β 1-4 ) in the Golgi apparatus (2), a process that enhances the kinetics and membrane localization of Na V channels (3, 4). In addition to these roles, several Na V β subunits also function as cell adhesion molecules independent of Na V channels (5). At the axon initial segment (AIS) and nodes of Ranvier of neurons, Na V channels form clusters that facilitate the generation and propagation of action potentials. Although the molecular basis of Na V clustering at these sites has been extensively studied (6), the transport of Na V channels to these sites has been less explored. For instance, to date, only the annexin II light chain (p11) has been shown to associate with and facilitate the transport of Na V 1.8 to the plasma membrane (7). Furthermore, subsequent efforts revealed that p11 acts only on Na V 1.8 (8). Thus, the transport of other Na V channels remains unclear.In zebrafish, several studies have explored the contribution of Na V channels and their auxiliary Na V β subunits through the use of forward and reverse genetics. In brief, impairments in Na V 1.1, Na V 1.6a, and Na V β 1b have been shown to diminish touch-evoked escape responses and Na V channel activity in Rohon-Beard (RB) sensory neurons (9-11). In addition, two other mutants identified in forward genetic screens have been shown to affect Na V channel activity indirectly. The first, pigu, arises from a mutation in a GPItransamidase necessary for the proper localization of Na V channels (12). Although the genetic locus of the second mutation, macho (13,14), has yet to be identified, rough mapping indicates that it lies with...

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Section: Discussionmentioning

confidence: 59%

RING finger protein 121 facilitates the degradation and membrane localization of voltage-gated sodium channels

Ogino

Low

Yamada

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Nav1.1lb belongs to a family of at least eight voltage-gated sodium channels encoded in the vertebrate genome (Novak et al, 2006). Although its mutation causes a rather specific behavioral defect, we found that this channel is expressed rather broadly in the CNS.…”

Section: Discussionmentioning

confidence: 67%

“…This was confirmed by quantitative PCR (data not shown). Similar to other voltage-gated sodium channels (Novak et al, 2006), the gene is broadly expressed in the brain (Fig. 10).…”

Section: Genetic and Functional Identification Of Didy S552 As A Nullmentioning

confidence: 89%

See 1 more Smart Citation

Optogenetic Localization and Genetic Perturbation of Saccade-Generating Neurons in Zebrafish

Schoonheim

Arrenberg²,

Bene³

et al. 2010

J. Neurosci.

164

156

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The optokinetic response (OKR) to a visual stimulus moving at constant velocity consists of a series of two alternating components, a slow phase, during which the eyes follow the stimulus, and a quick phase, which resets the eyes to begin a new response cycle. The quick phases of the OKR resemble the saccades observed during free viewing. It is unclear to what extent the premotor circuitry underlying these two types of jerky, conjugate eye movements is conserved among vertebrates. Zebrafish (Danio rerio) larvae, broadly expressing halorhodopsin (NpHR) or channelrhodopsin-2 (ChR2) in most neurons, were used to map the location of neurons involved in this behavior. By blocking activity in localized groups of NpHR-expressing neurons with an optic fiber positioned above the head of the fish and by systematically varying the site of photostimulation, we discovered that activity in a small hindbrain area in rhombomere 5 was necessary for saccades to occur. Unilateral block of activity at this site affected behavior in a direction-specific manner. Inhibition of the right side suppressed rightward saccades of both eyes, while leaving leftward saccades unaffected, and vice versa. Photostimulation of this area in ChR2-transgenic fish was sufficient to trigger saccades that were precisely locked to the light pulses. These extra saccades could be induced both during free viewing and during the OKR, and were distinct in their kinetics from eye movements elicited by stimulating the abducens motor neurons. Zebrafish double indemnity (didy) mutants were identified in a chemical mutagenesis screen based on a defect in sustaining saccades during OKR. Positional cloning, molecular analysis, and electrophysiology revealed that the didy mutation disrupts the voltage-gated sodium channel Scn1lab (Nav1.lb). ChR2 photostimulation of the putative hindbrain saccade generator was able to fully reconstitute saccades in the didy mutant. Our studies demonstrate that an optogenetic approach is useful for targeted loss-offunction and gain-of-function manipulations of neural circuitry underlying eye movements in zebrafish and that the saccade-generating circuit in this species shares many of its properties with that in mammals.

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“…The involvement of voltage-gated Na 1 channels in zebrafish embryos and larvae was reported by Novak et al (2006), who showed the embryonic and larval expression patterns for eight members of the gene family (scna) coding for zebrafish Na 1 channels proteins.…”

mentioning

confidence: 93%

Ion currents in embryo development

Tosti

Boni

Gallo

2016

Birth Defects Research Pt C

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Ion channels are proteins expressed in the plasma membrane of electrogenic cells. In the zygote and blastomeres of the developing embryo, electrical modifications result from ion currents that flow through these channels. This phenomenon implies that ion current activity exerts a specific developmental function, and plays a crucial role in signal transduction and the control of embryogenesis, from the early cleavage stages and during growth and development of the embryo. This review describes the involvement of ion currents in early embryo development, from marine invertebrates to human, focusing on the occurrence, modulation, and dynamic role of ion fluxes taking place on the zygote and blastomere plasma membrane, and at the intercellular communication between embryo cell stages.Birth Defects Research (Part C) 108:6-18, 2016.V C 2016 Wiley Periodicals, Inc.

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Embryonic and larval expression of zebrafish voltage‐gated sodium channel α‐subunit genes

Cited by 81 publications

References 60 publications

RING finger protein 121 facilitates the degradation and membrane localization of voltage-gated sodium channels

RING finger protein 121 facilitates the degradation and membrane localization of voltage-gated sodium channels

Optogenetic Localization and Genetic Perturbation of Saccade-Generating Neurons in Zebrafish

Ion currents in embryo development

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