Decoding of Polymodal Sensory Stimuli by Postsynaptic Glutamate Receptors in C. elegans

Mellem, Jerry E.; Brockie, Penelope J.; Zheng, Yi; Madsen, David M.; Maricq, Andres V.

doi:10.1016/s0896-6273(02)01088-7

Cited by 151 publications

(277 citation statements)

References 32 publications

Supporting

Mentioning

251

Contrasting

Order By: Relevance

“…The levels of GLR-1 on the postsynaptic membrane can be monitored through changes in behavior (Burbea et al, 2002;Juo and Kaplan, 2004). C. elegans spend the majority of their time moving forward; however, this forward locomotion is occasionally halted by spontaneous reversals in the direction of movement, and GLR-1 signaling positively regulates these spontaneous reversals (Zheng et al, 1999;Mellem et al, 2002). C. elegans backward locomotion can also be induced by stimulating the mechanosensory neuron ASH, which makes glutamatergic connections to the GLR-1-expressing interneurons (White et al, 1986;Kaplan and Horvitz, 1993).…”

Section: Kel-8 Negatively Regulates Glr-1 Functionmentioning

confidence: 99%

“…GLR-1 is expressed in interneurons, where it functions to mediate nose-touch mechanosensation and regulate the frequency of spontaneous reversals in locomotion (Hart et al, 1995;Maricq et al, 1995;Brockie et al, 2001). Mutants lacking GLR-1 are nose-touch defective and rarely reverse direction, whereas nematodes with elevated GLR-1 activity reverse direction at an increased frequency (Hart et al, 1995;Maricq et al, 1995;Zheng et al, 1999;Brockie et al, 2001;Mellem et al, 2002). Chimeric GLR-1 receptors tagged with the green fluorescent protein (GLR-1::GFP) are used to visualize glutamate receptors in living animals; these chimeric receptors are functional because they fully rescue glr-1 mutants (Rongo et al, 1998;Rongo and Kaplan, 1999).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

KEL-8 Is a Substrate Receptor for CUL3-dependent Ubiquitin Ligase That Regulates Synaptic Glutamate Receptor Turnover

Schaefer

Rongo

2006

MBoC

View full text Add to dashboard Cite

The regulated localization of ␣-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors (AMPARs) to synapses is an important component of synaptic signaling and plasticity. Regulated ubiquitination and endocytosis determine the synaptic levels of AMPARs, but it is unclear which factors conduct these processes. To identify genes that regulate AMPAR synaptic abundance, we screened for mutants that accumulate high synaptic levels of the AMPAR subunit GLR-1 in Caenorhabditis elegans. GLR-1 is localized to postsynaptic clusters, and mutants for the BTB-Kelch protein KEL-8 have increased GLR-1 levels at clusters, whereas the levels and localization of other synaptic proteins seem normal. KEL-8 is a neuronal protein and is localized to sites adjacent to GLR-1 postsynaptic clusters along the ventral cord neurites. KEL-8 is required for the ubiquitin-mediated turnover of GLR-1 subunits, and kel-8 mutants show an increased frequency of spontaneous reversals in locomotion, suggesting increased levels of GLR-1 are present at synapses. KEL-8 binds to CUL-3, a Cullin 3 ubiquitin ligase subunit that we also find mediates GLR-1 turnover. Our findings indicate that KEL-8 is a substrate receptor for Cullin 3 ubiquitin ligases that is required for the proteolysis of GLR-1 receptors and suggest a novel postmitotic role in neurons for Kelch/CUL3 ubiquitin ligases. INTRODUCTIONGlutamate is the most abundant excitatory neurotransmitter in the brain, and glutamatergic synapses play a critical role in learning, memory, and developmental plasticity of the central nervous system (Meldrum, 2000). Ionotropic glutamate receptors (GluRs) receive and transduce glutamatergic signals on the postsynaptic face of synapses, where these multitransmembrane spanning proteins assemble into tetrameric glutamate-gated channels of differing subunit composition (Hollmann and Heinemann, 1994;Dingledine et al., 1999). The regulation of these receptors, the ␣-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) type in particular, is a critical mechanism by which neurons modulate synaptic strength (Bredt and Nicoll, 2003;Malenka, 2003;Malinow, 2003;Sheng and Hyoung Lee, 2003). In addition, GluRs play a role in several diseases of the nervous system, ranging from neurodegeneration to drug addiction and schizophrenia (Tzschentke, 2002;Mattson, 2003;Moghaddam, 2003;Aarts and Tymianski, 2004). To better understand how AMPA-type GluRs (AMPARs) function in the nervous system, it is essential to determine how the synaptic level and activity of AMPARs are regulated.AMPAR synaptic levels are controlled by proteins that interact with signaling elements on the carboxy-terminal tail sequences that are exposed to the cytosol (Dong et al., 1997;Rongo et al., 1998;Song et al., 1998;Srivastava et al., 1998;Xia et al., 1999;Sans et al., 2001). Although some of the tail sequence signaling elements function to maintain high levels of AMPARs at the synapse, other signaling elements recruit factors that result in the ubiquitination, endocytosis, ...

show abstract

Section: Kel-8 Negatively Regulates Glr-1 Functionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

KEL-8 Is a Substrate Receptor for CUL3-dependent Ubiquitin Ligase That Regulates Synaptic Glutamate Receptor Turnover

Schaefer

Rongo

2006

MBoC

View full text Add to dashboard Cite

show abstract

“…Furthermore, GLR-1 is required at interneurons that are part of a simple sensory circuit regulating backward movement, both in response to nose-touch stimulus and as part of the foraging behavior of animals. Mutants with depressed GLR-1 synaptic levels are nosetouch defective and rarely reverse direction, whereas mutants with elevated synaptic levels reverse direction with increased frequency (Hart et al, 1995;Maricq et al, 1995;Zheng et al, 1999;Brockie et al, 2001b;Mellem et al, 2002;Schaefer and Rongo, 2006). Therefore, by observing the behavior (e.g., nose-touch response and reversals per minute) of animals with different genetic backgrounds, we can compare signal strength at this circuit, and we can infer the abundance of GLR-1 AMPARs present at the postsynaptic plasma membrane.…”

mentioning

confidence: 99%

“…If mutations in rab-10 or lin-10 result in the accumulation of GLR-1 at an internal membrane trafficking compartment, then these mutations should result in corresponding GLR-1-mediated behavioral phenotypes (Burbea et al, 2002;Juo and Kaplan, 2004;Shim et al, 2004;Umemura et al, 2005;Schaefer and Rongo, 2006). In C. elegans, GLR-1 signaling positively regulates spontaneous reversals during forward locomotion as animals forage for food (Mellem et al, 2002;Zheng et al, 2004). Backward locomotion in C. elegans can also be induced by stimulating the mechanosensory neuron ASH, which makes glutamatergic connections to the GLR-1-expressing interneurons Figure 1.…”

mentioning

confidence: 99%

“…18, November 2007 4389 (White et al, 1986;Kaplan and Horvitz, 1993). Mutants with reduced GLR-1 activity have a lower frequency of spontaneous reversals and are nose-touch insensitive, whereas mutants with increased GLR-1 activity (e.g., higher levels of synaptic GLR-1 at the cell surface) have a higher frequency of spontaneous reversals (Hart et al, 1995;Maricq et al, 1995;Burbea et al, 2002;Mellem et al, 2002;Juo and Kaplan, 2004;Shim et al, 2004;Zheng et al, 2004;Umemura et al, 2005;Schaefer and Rongo, 2006). We examined GLR-1-mediated behaviors in wild-type animals and in animals with mutations in lin-10 and rab-10.…”

mentioning

confidence: 99%

See 1 more Smart Citation

RAB-10 Regulates Glutamate Receptor Recycling in a Cholesterol-dependent Endocytosis Pathway

Glodowski

Chen

Schaefer

et al. 2007

MBoC

104

View full text Add to dashboard Cite

Regulated endocytosis of ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs) is critical for synaptic plasticity. However, the specific combination of clathrin-dependent and -independent mechanisms that mediate AMPAR trafficking in vivo have not been fully characterized. Here, we examine the trafficking of the AMPAR subunit GLR-1 in Caenorhabditis elegans. GLR-1 is localized on synaptic membranes, where it regulates reversals of locomotion in a simple behavioral circuit. Animals lacking RAB-10, a small GTPase required for endocytic recycling of intestinal cargo, are similar in phenotype to animals lacking LIN-10, a postsynaptic density 95/disc-large/zona occludensdomain containing protein: GLR-1 accumulates in large accretions and animals display a decreased frequency of reversals. Mutations in unc-11 (AP180) or itsn-1 (Intersectin 1), which reduce clathrin-dependent endocytosis, suppress the lin-10 but not rab-10 mutant phenotype, suggesting that LIN-10 functions after clathrin-mediated endocytosis. By contrast, cholesterol depletion, which impairs lipid raft formation and clathrin-independent endocytosis, suppresses the rab-10 but not the lin-10 phenotype, suggesting that RAB-10 functions after clathrin-independent endocytosis. Animals lacking both genes display additive GLR-1 trafficking defects. We propose that RAB-10 and LIN-10 recycle AMPARs from intracellular endosomal compartments to synapses along distinct pathways, each with distinct sensitivities to cholesterol and the clathrin-mediated endocytosis machinery. INTRODUCTIONContinuous movement of ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs) into and out of synaptic membranes is a key mechanism for the regulation of excitatory synaptic strength. Previous work has shown that insertion of AMPARs into the plasma membrane strengthens synapses and that it is required to convert silent synapses into active synapses (Bredt and Nicoll, 2003;Malenka, 2003;Malinow, 2003;Sheng and Hyoung Lee, 2003;Gerges et al., 2005). Furthermore, it has recently been shown that recycling of AMPARs from internal endosomal compartments back to the plasma membrane is important for long-term potentiation (Park et al., 2004). By contrast, endocytosis of AMPARs at sites adjacent to the postsynaptic density is important for long-term depression (Carroll et al., 2001;Racz et al., 2004). Thus, molecular machinery required for endocytosis, as well as intracellular membrane trafficking processes, ultimately regulates the character of signal transmitted at each synapse.Multiple endocytosis trafficking pathways have been observed in cells. Clathrin-dependent endocytosis occurs at clathrin-coated pits, where transmembrane protein cargo and adaptor molecules recruit soluble clathrin (Le Roy and Wrana, 2005). Vesicles coated with a clathrin lattice are then pinched off from the membrane. Members of the Rab family of small guanosine triphosphate (GTP)ases mediate the intracellular membrane trafficking of endocytose...

show abstract

High‐Throughput Analysis of Behavior Under the Control of Optogenetics in Caenorhabditis elegans

McDiarmid

Ardiel

et al. 2018

CP Neuroscience

View full text Add to dashboard Cite

In this unit, we describe an inexpensive and versatile method for optogenetic stimulation of a large population of genetically engineered Caenorhabditis elegans worms while quantitatively analyzing behavior. A custom light‐emitting diode light source is used to deliver blue‐light stimuli, causing direct depolarization of neurons expressing the light‐gated cation channel Channelrhodopsin‐2, which in turn evokes behavioral responses. The behavioral responses are recorded by a high‐throughput machine vision–based tracking system, the Multi‐Worm Tracker, for detailed analysis. This approach allows researchers to bypass technical obstacles to simultaneously deliver uniform stimuli to a large number of freely behaving animals and investigate the neural underpinnings of behavior. © 2018 by John Wiley & Sons, Inc.

show abstract

Decoding of Polymodal Sensory Stimuli by Postsynaptic Glutamate Receptors in C. elegans

Cited by 151 publications

References 32 publications

KEL-8 Is a Substrate Receptor for CUL3-dependent Ubiquitin Ligase That Regulates Synaptic Glutamate Receptor Turnover

KEL-8 Is a Substrate Receptor for CUL3-dependent Ubiquitin Ligase That Regulates Synaptic Glutamate Receptor Turnover

RAB-10 Regulates Glutamate Receptor Recycling in a Cholesterol-dependent Endocytosis Pathway

High‐Throughput Analysis of Behavior Under the Control of Optogenetics in Caenorhabditis elegans

Contact Info

Product

Resources

About