Locomotion Behavior Is Affected by the GαS Pathway and the Two-Pore-Domain K+ Channel TWK-7 Interacting in GABAergic Motor Neurons in Caenorhabditis elegans

In the nervous system, a perfect balance of excitation and inhibition is required, for example, to enable coordinated locomotion. In Caenorhabditis elegans, cholinergic and GABAergic motor neurons (MNs) effect waves of contralateral muscle contraction and relaxation. Cholinergic MNs innervate muscle as well as GABAergic MNs, projecting to the opposite side of the body, at dyadic synapses. Only a few connections exist from GABAergic to cholinergic MNs, emphasizing that GABA signaling is mainly directed toward muscle. Yet, a GABAB receptor comprising GBB-1 and GBB-2 subunits, expressed in cholinergic MNs, was shown to affect locomotion, likely by feedback inhibition of cholinergic MNs in response to spillover GABA. In the present study, we examined whether the GBB-1/2 receptor could also affect short-term plasticity in cholinergic MNs with the use of channelrhodopsin-2-mediated photostimulation of GABAergic and cholinergic neurons. The GBB-1/2 receptor contributes to acute body relaxation, evoked by photoactivation of GABAergic MNs, and to effects of GABA on locomotion behavior. Loss of the plasma membrane GABA transporter SNF-11, as well as acute photoevoked GABA release, affected cholinergic MN function in opposite directions. Prolonged stimulation of GABA MNs had subtle effects on cholinergic MNs, depending on stimulus duration and gbb-2. Thus GBB-1/2 receptors serve mainly for linear feedback inhibition of cholinergic MNs but also evoke minor plastic changes.

Download Full-text

Complex Locomotion Behavior Changes Are Induced in Caenorhabditis elegans by the Lack of the Regulatory Leak K+ Channel TWK-7

Genetics ◽

10.1534/genetics.116.188896 ◽

2016 ◽

Vol 204 (2) ◽

pp. 683-701 ◽

Cited By ~ 4

Author(s):

K. Luersen ◽

D.-C. Gottschling ◽

F. Doring

Keyword(s):

Caenorhabditis Elegans ◽

K Channel ◽

Behavior Changes ◽

Locomotion Behavior

Download Full-text

Faculty Opinions recommendation of Tandem pore domain halothane-inhibited K+ channel subunits THIK1 and THIK2 assemble and form active channels.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718541814.793500211 ◽

2014 ◽

Author(s):

Douglas Bayliss

Keyword(s):

K Channel ◽

Active Channels ◽

Pore Domain

Download Full-text

The Caenorhabditis elegans odr-2 Gene Encodes a Novel Ly-6-Related Protein Required for Olfaction

Genetics ◽

10.1093/genetics/157.1.211 ◽

2001 ◽

Vol 157 (1) ◽

pp. 211-224 ◽

Cited By ~ 1

Author(s):

Joseph H Chou ◽

Cornelia I Bargmann ◽

Piali Sengupta

Keyword(s):

Caenorhabditis Elegans ◽

Motor Neurons ◽

Amino Terminus ◽

Signaling Proteins ◽

Related Protein ◽

Olfactory Neurons ◽

Unique Role ◽

C Elegans ◽

Founding Member ◽

High Concentrations

Abstract Caenorhabditis elegans odr-2 mutants are defective in the ability to chemotax to odorants that are recognized by the two AWC olfactory neurons. Like many other olfactory mutants, they retain responses to high concentrations of AWC-sensed odors; we show here that these residual responses are caused by the ability of other olfactory neurons (the AWA neurons) to be recruited at high odor concentrations. odr-2 encodes a membrane-associated protein related to the Ly-6 superfamily of GPI-linked signaling proteins and is the founding member of a C. elegans gene family with at least seven other members. Alternative splicing of odr-2 yields three predicted proteins that differ only at the extreme amino terminus. The three isoforms have different promoters, and one isoform may have a unique role in olfaction. An epitope-tagged ODR-2 protein is expressed at high levels in sensory neurons, motor neurons, and interneurons and is enriched in axons. The AWC neurons are superficially normal in their development and structure in odr-2 mutants, but their function is impaired. Our results suggest that ODR-2 may regulate AWC signaling within the neuronal network required for chemotaxis.

Download Full-text

A Network of HSPG Core Proteins and HS Modifying Enzymes Regulates Netrin-Dependent Guidance of D-Type Motor Neurons in Caenorhabditis elegans

PLoS ONE ◽

10.1371/journal.pone.0074908 ◽

2013 ◽

Vol 8 (9) ◽

pp. e74908 ◽

Cited By ~ 14

Author(s):

Stephan Gysi ◽

Christa Rhiner ◽

Stephane Flibotte ◽

Donald G. Moerman ◽

Michael O. Hengartner

Keyword(s):

Caenorhabditis Elegans ◽

Motor Neurons ◽

Core Proteins ◽

Type Motor

Download Full-text

The MADD-3 LAMMER Kinase Interacts with a p38 MAP Kinase Pathway to Regulate the Display of the EVA-1 Guidance Receptor in Caenorhabditis elegans

PLoS Genetics ◽

10.1371/journal.pgen.1006010 ◽

2016 ◽

Vol 12 (4) ◽

pp. e1006010 ◽

Cited By ~ 5

Author(s):

Serena A. D’Souza ◽

Luckshi Rajendran ◽

Rachel Bagg ◽

Louis Barbier ◽

Derek M. van Pel ◽

...

Keyword(s):

Plasma Membrane ◽

Caenorhabditis Elegans ◽

Map Kinase ◽

Motor Neurons ◽

Leading Edge ◽

P38 Map Kinase ◽

Endosomal Trafficking ◽

Guidance Cue ◽

Map Kinase Pathway ◽

Kinase Pathway

The proper display of transmembrane receptors on the leading edge of migrating cells and cell extensions is essential for their response to guidance cues. We previously discovered that MADD-4, which is an ADAMTSL secreted by motor neurons in Caenorhabditis elegans, interacts with an UNC-40/EVA-1 co-receptor complex on muscles to attract plasma membrane extensions called muscle arms. In nematodes, the muscle arm termini harbor the post-synaptic elements of the neuromuscular junction. Through a forward genetic screen for mutants with disrupted muscle arm extension, we discovered that a LAMMER kinase, which we call MADD-3, is required for the proper display of the EVA-1 receptor on the muscle’s plasma membrane. Without MADD-3, EVA-1 levels decrease concomitantly with a reduction of the late-endosomal marker RAB-7. Through a genetic suppressor screen, we found that the levels of EVA-1 and RAB-7 can be restored in madd-3 mutants by eliminating the function of a p38 MAP kinase pathway. We also found that EVA-1 and RAB-7 will accumulate in madd-3 mutants upon disrupting CUP-5, which is a mucolipin ortholog required for proper lysosome function. Together, our data suggests that the MADD-3 LAMMER kinase antagonizes the p38-mediated endosomal trafficking of EVA-1 to the lysosome. In this way, MADD-3 ensures that sufficient levels of EVA-1 are present to guide muscle arm extension towards the source of the MADD-4 guidance cue.

Download Full-text

Identification Of A Novel Gene Altered In The RQ1 Mutant Strain Affecting Motor Axon Migration In Caenorhabditis Elegans

10.32920/ryerson.14662620 ◽

2021 ◽

Author(s):

Haider Z. Naqvi

Keyword(s):

Caenorhabditis Elegans ◽

Axon Guidance ◽

Motor Neurons ◽

Genetic Background ◽

Germ Line ◽

Strong Indication ◽

Wild Type ◽

C Elegans ◽

Novel Gene ◽

Mutation Region

Novel genetic enhancer screens were conducted targeting mutants involved in the guidance of axons of the DA and DB classes of motor neurons in C. elegans. These mutations are expected in genes that function in parallel to the unc-g/Netrin pathway. The screen was conducted in an unc-5(e53) genetic background and enhancers of the axon guidance defects caused by the absence of UNC-5 were identified. Three mutants were previously identified in the screen called rq1, rq2 and rq3 and two additional mutants called H2-4 and M1-3, were isolated in this study. In order to identify the gene affected by the rq1 mutation, wild-type copies of genes in the mapped rq1 mutation region were injected into the mutants to rescue the phenotypic defects. This is a strong indication that the gene of interest is a novel gene called H04D03.1. Promising results indicate that the H04D03.1 protein also works in germ-line apoptosis.

Download Full-text

Structural Basis for pH-Gating of the K+ Channel TWIK1 at the Selectivity Filter

10.1101/2021.11.09.467928 ◽

2021 ◽

Author(s):

Toby S Turney ◽

Vivian Li ◽

Stephen G Brohawn

Keyword(s):

Conformational Changes ◽

Pancreatic Beta Cells ◽

Low Ph ◽

Selectivity Filter ◽

Structural Basis ◽

K Channel ◽

Open Conformation ◽

Gating Mechanism ◽

Lipid Nanodiscs ◽

Pore Domain

TWIK1 is a widely expressed pH-gated two-pore domain K+ channel (K2P) that contributes to cardiac rhythm generation and insulin release from pancreatic beta cells. TWIK1 displays unique properties among K2Ps including low basal activity and inhibition by extracellular protons through incompletely understood mechanisms. Here, we present cryo-EM structures of TWIK1 in lipid nanodiscs at high and low pH that reveal a novel gating mechanism at the K+ selectivity filter. At high pH, TWIK1 adopts an open conformation. At low pH, protonation of an extracellular histidine results in a cascade of conformational changes that close the channel by sealing the top of the selectivity filter, displacing the helical cap to block extracellular ion access pathways, and opening gaps for lipid block of the intracellular cavity. These data provide a mechanistic understanding for extracellular pH-gating of TWIK1 and show how diverse mechanisms have evolved to gate the selectivity filter of K+ channels.

Download Full-text

Modulation of the Two-pore Domain Acid-sensitive K+Channel TASK-2 (KCNK5) by Changes in Cell Volume

Journal of Biological Chemistry ◽

10.1074/jbc.m107192200 ◽

2001 ◽

Vol 276 (46) ◽

pp. 43166-43174 ◽

Cited By ~ 113

Author(s):

Marı́a Isabel Niemeyer ◽

L. Pablo Cid ◽

L. Felipe Barros ◽

Francisco V. Sepúlveda

Keyword(s):

Cell Volume ◽

K Channel ◽

Pore Domain

Download Full-text

Cerebrovascular responses in mice deficient in the potassium channel, TREK-1

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00057.2010 ◽

2010 ◽

Vol 299 (2) ◽

pp. R461-R469 ◽

Cited By ~ 21

Author(s):

Khodadad Namiranian ◽

Eric E. Lloyd ◽

Randy F. Crossland ◽

Sean P. Marrelli ◽

George E. Taffet ◽

...

Keyword(s):

Arachidonic Acid ◽

Linolenic Acid ◽

Basilar Artery ◽

Cerebral Arteries ◽

K Channel ◽

Whole Cell ◽

Middle Cerebral Arteries ◽

Basilar Arteries ◽

Cerebrovascular Smooth Muscle Cells ◽

Pore Domain

We tested the hypothesis that TREK-1, a two-pore domain K channel, is involved with dilations in arteries. Because there are no selective activators or inhibitors of TREK-1, we generated a mouse line deficient in TREK-1. Endothelium-mediated dilations were not different in arteries from wild-type (WT) and TREK-1 knockout (KO) mice. This includes dilations of the middle cerebral artery to ATP, dilations of the basilar artery to ACh, and relaxations of the aorta to carbachol, a cholinergic agonist. The nitric oxide (NO) and endothelium-dependent hyperpolarizing factor components of ATP dilations were identical in the middle cerebral arteries of WT and TREK-1 KO mice. Furthermore, the NO and cyclooxygenase-dependent components were identical in the basilar arteries of the different genotypes. Dilations of the basilar artery to α-linolenic acid, an activator of TREK-1, were not affected by the absence of TREK-1. Whole cell currents recorded using patch-clamp techniques were similar in cerebrovascular smooth muscle cells (CVSMCs) from WT and TREK-1 KO mice. α-linolenic acid or arachidonic acid increased whole cell currents in CVSMCs from both WT and TREK-1 KO mice. The selective blockers of large-conductance Ca-activated K channels, penitrem A and iberiotoxin, blocked the increased currents elicited by either α-linolenic or arachidonic acid. In summary, dilations were similar in arteries from WT and TREK-1 KO mice. There was no sign of TREK-1-like currents in CVSMCs from WT mice, and there were no major differences in currents between the genotypes. We conclude that regulation of arterial diameter is not altered in mice lacking TREK-1.

Download Full-text