Coordinated Transcriptional Regulation of theunc-25Glutamic Acid Decarboxylase and theunc-47GABA Vesicular Transporter by theCaenorhabditis elegansUNC-30 Homeodomain Protein

Eastman, Catharine; Horvitz, H. Robert; Jin, Yishi

doi:10.1523/jneurosci.19-15-06225.1999

Cited by 163 publications

(149 citation statements)

References 47 publications

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“…We took advantage of the fact that unc-25 promoter activity in the DD and VD neurons is silenced in an unc-30 Ϫ/Ϫ background to visualize the AVL neuron (Eastman et al, 1999). We found that AVL, which normally projects an unbranched axon from a cell body located in the head to its target in the tail, displays inappropriate branches at the vulva in png-1 mutants (25% in cy9; n ϭ 150) (Fig.…”

Section: Png-1 Mutants Display An Increase In Axonal Branching Along mentioning

confidence: 98%

TheN-Glycanasepng-1Acts to Limit Axon Branching during Organ Formation in Caenorhabditis elegans

Habibi-Babadi

Su²,

Carvalho³

et al. 2010

J. Neurosci.

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Peptide:N-glycanases (PNGases) are cytoplasmic de-N-glycosylation enzymes that have been shown in cultured cells to facilitate the degradation of misfolded glycoproteins during endoplasmic reticulum-associated degradation and in the processing of major histocompatibility complex class I antigens for proper cell-surface presentation. The gene encoding PNGase activity was initially described in budding yeast (Png1p) and shown to be highly conserved from yeast to humans, but physiological roles in higher organisms have not been elucidated. Here we describe peripheral nervous system defects associated with the first loss-of-function mutations in an animal PNGase. Mutations in png-1, the Caenorhabditis elegans PNGase ortholog, result in an increase in axon branching during morphogenesis of the vulval egg-laying organ and egg-laying behavior changes. Neuronal defects include an increase in the branched morphology of the VC4 and VC5 egg-laying neurons as well as inappropriate branches from axons that run adjacent to the vulva but would normally remain unbranched. We show that png-1 is widely expressed and can act from both neurons and epithelial cells to restrict axon branching. A deletion allele of the DNA repair gene rad-23, orthologs of which are known to physically interact with PNGases in yeast and mammals, displays similar axon branching defects and genetic interactions with png-1. In summary, our analysis reveals a novel developmental role for a PNGase and Rad-23 in the regulation of neuronal branching during organ innervation.

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Section: Png-1 Mutants Display An Increase In Axonal Branching Along mentioning

confidence: 98%

TheN-Glycanasepng-1Acts to Limit Axon Branching during Organ Formation in Caenorhabditis elegans

Habibi-Babadi

Su²,

Carvalho³

et al. 2010

J. Neurosci.

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“…Ubiquitous expression of the UNC-30 protein led to the ectopic synthesis of GABA in many non-GABA neurons as well as in some non-neuronal tissues. UNC-30 was shown to bind to promoter elements in both the unc-25 (GAD-encoding) and unc-47 (VGAT-encoding) genes, and these elements were necessary for DD and VD neuronal expression [37]. Therefore, UNC-30 is required for GABA neuronal specification in the D-type neurons.…”

Section: Unc-47: What Protein Is the Vesicular Gaba Transporter?mentioning

confidence: 99%

The GABA nervous system in C. elegans

Schuske

Beg

Jørgensen

2004

Trends in Neurosciences

164

151

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GABA neurotransmission requires a specialized set of proteins to synthesize, transport or respond to GABA. This article reviews results from a genetic strategy in the nematode Caenorhabditis elegans designed to identify the genes responsible for these activities. These studies identified mutations in genes encoding five different proteins: the biosynthetic enzyme for GABA, the vesicular GABA transporter, a transcription factor that determines GABA neuron identity, a classic inhibitory GABA receptor and a novel excitatory GABA receptor. This review discusses the strategy employed to identify these genes as well as the conclusions about GABA transmission derived from study of the mutant phenotypes.Activity in the vertebrate brain depends on a yin and yang balance between excitatory and inhibitory neurotransmission. A deficit of excitatory neurotransmission will lead to unconsciousness; a deficit of inhibitory neurotransmission will lead to epileptic seizures. The most abundant inhibitory neurotransmitter in the brain is GABA. Normal GABA function requires specialized proteins such as biosynthetic enzymes, transporters and receptors. Defects in these proteins can lead to a specific imbalance of GABA neurotransmission and lead to diseases. For example, mutations in the a1 and g2 GABA receptor subunits can cause familial forms of epilepsy [1 -3].Over ten years ago, a strategy was devised to identify the proteins specialized for GABA function using a genetic approach in the nematode Caenorhabditis elegans [4,5]. These studies have lead to some important discoveries. Specifically, the vesicular GABA transporter (VGAT) was first discovered in C. elegans and this sequence was used to identify the mammalian homolog [6]. The homeodomain protein UNC-30 identified a class of transcription factors required for multiple aspects of GABA neuron identity [7,8]. These studies also revealed the first cation-selective GABA receptor [9]. This review will discuss first the strategy used to identify proteins required for GABA neurotransmission in C. elegans and then the impact that their discovery has had on our understanding of GABA function. StrategyTo define the proteins required for GABA function, McIntire and colleagues looked for mutations in the nematode C. elegans that specifically disrupted GABAmediated behaviors [4,5]. To identify the GABA-containing cells in C. elegans, animals were stained using antibodies against the neurotransmitter. Antibody staining revealed that 26 of the 302 neurons present in C. elegans express the neurotransmitter GABA (Figure 1a). These 26 GABApositive neurons comprise six DD neurons, 13 VD neurons, four RME neurons, an RIS neuron, an AVL neuron and a DVB neuron (Figure 1b). These neurons fall into different classes based on their synaptic outputs: the D-type neurons -that is, the DD and VD motor neuronsinnervate the dorsal and ventral body muscles, respectively; the RME motor neurons innervate the head muscles; the AVL and DVB motor neurons innervate the enteric muscles; and RIS is an interneuron ...

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“…All transgenic lines were generated using standard methods (Mello et al 1991), and all constructs were derived from the pPD49.26 vector (Addgene) using standard subcloning procedures. acr-2 is a cholinergic neuron-specific promoter (Nurrish et al 1999), and unc-47 is a GABAergic neuron-specific promoter (Eastman et al 1999). For the double transgenic animals noted in Figure 3C, an acr-2::GFP construct (pCL31) was coinjected with pL15EK (both at 50 ng/ml) into the strain MT8189, and GFP-positive animals were identified and mated with unc-47::mCherry-expressing males [strain IZ501(UfIs34), a generous gift from M. Francis].…”

Section: Transgenic Animalsmentioning

confidence: 99%

“…Expression of the acr-2::DOP-3 transgene in dat-1(ok157); dop-3(vs106) double mutants partially rescued dat-1-dependent SWIP, such that only 50% of animals were moving compared to 88% for empty vector controls ( Figure 3C). Because the DOP-3 receptor is also expressed in the GABAergic motor neurons (Chase et al 2004), we expressed the DOP-3 receptor in the GABAergic neurons using the unc-47 promoter (Eastman et al 1999). This also resulted in partial rescue of paralysis (68% of animals moving compared to 96% for empty vector control).…”

Section: )mentioning

confidence: 99%

Coexpressed D1- and D2-Like Dopamine Receptors Antagonistically Modulate Acetylcholine Release in Caenorhabditis elegans

Allen¹,

Maher

Wani

et al. 2011

Genetics

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Dopamine acts through two classes of G protein-coupled receptor (D1-like and D2-like) to modulate neuron activity in the brain. While subtypes of D1-and D2-like receptors are coexpressed in many neurons of the mammalian brain, it is unclear how signaling by these coexpressed receptors interacts to modulate the activity of the neuron in which they are expressed. D1-and D2-like dopamine receptors are also coexpressed in the cholinergic ventral-cord motor neurons of Caenorhabditis elegans. To begin to understand how coexpressed dopamine receptors interact to modulate neuron activity, we performed a genetic screen in C. elegans and isolated mutants defective in dopamine response. These mutants were also defective in behaviors mediated by endogenous dopamine signaling, including basal slowing and swimming-induced paralysis. We used transgene rescue experiments to show that defects in these dopamine-specific behaviors were caused by abnormal signaling in the cholinergic motor neurons. To investigate the interaction between the D1-and D2-like receptors specifically in these cholinergic motor neurons, we measured the sensitivity of dopamine-signaling mutants and transgenic animals to the acetylcholinesterase inhibitor aldicarb. We found that D2 signaling inhibited acetylcholine release from the cholinergic motor neurons while D1 signaling stimulated release from these same cells. Thus, coexpressed D1-and D2-like dopamine receptors act antagonistically in vivo to modulate acetylcholine release from the cholinergic motor neurons of C. elegans.

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Coordinated Transcriptional Regulation of theunc-25Glutamic Acid Decarboxylase and theunc-47GABA Vesicular Transporter by theCaenorhabditis elegansUNC-30 Homeodomain Protein

Cited by 163 publications

References 47 publications

TheN-Glycanasepng-1Acts to Limit Axon Branching during Organ Formation in Caenorhabditis elegans

TheN-Glycanasepng-1Acts to Limit Axon Branching during Organ Formation in Caenorhabditis elegans

The GABA nervous system in C. elegans

Coexpressed D1- and D2-Like Dopamine Receptors Antagonistically Modulate Acetylcholine Release in Caenorhabditis elegans

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