The kinesin-3 family motor KLP-4 regulates anterograde trafficking of GLR-1 glutamate receptors in the ventral nerve cord of<i>Caenorhabditis elegans</i>

Monteiro, Michael I.; Ahlawat, Shikha; Kowalski, Jennifer R.; Malkin, Emily; Koushika, Sandhya P.; Juo, Peter

doi:10.1091/mbc.e12-04-0334

Cited by 40 publications

(34 citation statements)

References 82 publications

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“…Our data also suggest a critical role for the motor protein KIF3A in this mechanism. Previous studies demonstrated that various motor proteins of the KIFs exhibit differential function to form intracellular cargo apparatus and regulate protein trafficking, including that of the vascular endothelial growth factor receptor 2 in endothelial cells (34), the glutamate receptor in the ventral nerve cord of Caenorhabditis elegans (worms) (35), and voltage-gated potassium (K v ) channels in mouse hippocampal neurons (36). Specifically, KIF3A mediates the polarized trafficking of K v 1.2 channel to axons (37,38) and the transport of vesicles containing -catenin toward the plasma membrane in the developing neuroepithelium (39).…”

Section: Discussionmentioning

confidence: 99%

Palmitoylation of δ-catenin promotes kinesin-mediated membrane trafficking of Na _v 1.6 in sensory neurons to promote neuropathic pain

Zhang

Ding

et al. 2018

Sci. Signal.

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Palmitoylation of -catenin is critical to synapse plasticity and memory formation. We found that -catenin palmitoylation is also instrumental in the development of neuropathic pain. The abundances of palmitoylated -catenin and the palmitoyl acyltransferase DHHC3 were increased in dorsal root ganglion (DRG) sensory neurons in rat models of neuropathic pain. Inhibiting palmitoyl acyltransferases or decreasing -catenin abundance in the DRG by intrathecal injection of 2-bromopalmitate or shRNA, respectively, alleviated oxaliplatin or nerve injury-induced neuropathic pain in the rats. The palmitoylation of -catenin, which was induced by the inflammatory cytokine TNF-, facilitated its interaction with the voltage-gated sodium channel Na v 1.6 and the kinesin motor protein KIF3A, which promoted the trafficking of Na v 1.6 to the plasma membrane in DRG neurons and contributed to mechanical hypersensitivity and allodynia in rats. These findings suggest that a palmitoylation-mediated KIF3A/-catenin/Na v 1.6 complex enhances the transmission of mechanical and nociceptive signals; thus, blocking this mechanism may be therapeutic in patients with neuropathic pain.

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Section: Discussionmentioning

confidence: 99%

Palmitoylation of δ-catenin promotes kinesin-mediated membrane trafficking of Na _v 1.6 in sensory neurons to promote neuropathic pain

Zhang

Ding

et al. 2018

Sci. Signal.

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“…Signaling through GLR-1 controls the rate at which animals reverse during spontaneous locomotion (Zheng et al, 1999). Mutants with reduced glutamate signaling, such as glr-1 null mutants or animals lacking the vesicular glutamate transporter eat-4 /VGLUT, exhibit decreased reversal frequencies (Brockie et al, 2001; Burbea et al, 2002; Zheng et al, 1999), whereas mutants with increased GLR-1 signaling exhibit a higher rate of reversals (Burbea et al, 2002; Juo and Kaplan, 2004; Juo et al, 2007; Schaefer and Rongo, 2006; Zheng et al, 1999, Monteiro et al, 2012). We found that the spontaneous reversal frequency of daf-8 and daf-7 mutant animals is significantly higher than in wild type animals (Figure 7 A), consistent with increased signaling through GLR-1 receptors.…”

Section: Resultsmentioning

confidence: 99%

The DAF-7/TGF-β signaling pathway regulates abundance of the Caenorhabditis elegans glutamate receptor GLR-1

McGehee

Moss

Juo

2015

Molecular and Cellular Neuroscience

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Transforming growth factor-β (TGF-β) family signaling pathways have roles in both neuronal development and the regulation of synaptic function. Here we identify a novel role for the C. elegans DAF-7/TGF-β signaling pathway in the regulation of the AMPA-type glutamate receptor GLR-1. We found that the abundance of GLR-1 increases at synapses in the ventral nerve cord (VNC) of animals with loss-of-function mutations in multiple DAF-7/TGF-β pathway components including the TGF-β ligand DAF-7, the type I receptor DAF-1, and the Smads DAF-8 and DAF-14. The GLR-1 defect can be rescued by expression of daf-8 specifically in glr-1-expressing interneurons. The effect on GLR-1 was specific for the DAF-7 pathway because mutations in the DBL-1/TGF-β family pathway did not increase GLR-1 levels in the VNC. Immunoblot analysis indicates that total levels of GLR-1 protein are increased in neurons of DAF-7/TGF-β pathway mutants. The increased abundance of GLR-1 in the VNC of daf-7 pathway mutants is dependent on the transcriptional regulator DAF-3/Smad suggesting that DAF-3-dependent transcription controls GLR-1 levels. Furthermore, we found that glr-1 transcription is increased in daf-7 mutants based on a glr-1 transcriptional reporter. Together these results suggest that the DAF-7/TGF-β signaling pathway functions in neurons and negatively regulates the abundance of GLR-1, in part, by controlling transcription of the receptor itself. Finally, DAF-7/TGF-β pathway mutants exhibit changes in spontaneous locomotion that are dependent on endogenous GLR-1 and consistent with increased glutamatergic signaling. These results reveal a novel mechanism by which TGF-β signaling functions in the nervous system to regulate behavior.

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“…Cell cycle-independent roles of CDK5 have been identified in a mammalian nervous system (Su and Tsai 2011). Interestingly, C. elegans CDK-5 is also required for neuronal functions (Ou et al 2010; Park et al 2011; Goodwin et al 2012; Monteiro et al 2012). Further, C. elegans CDK-8 regulates axon navigation decisions in the nervous system (Steimel et al 2013).…”

Section: Discussionmentioning

confidence: 99%

“…In C. elegans , CDK-5 regulates polarized trafficking of presynaptic components and dense-core vesicles (Ou et al 2010; Goodwin et al 2012). CDK-5 is also required for synapse elimination and formation (Park et al 2011), and for trafficking of glutamate receptors in the ventral nerve cord (Monteiro et al 2012). CDK-8 is required for axon navigation decisions in neurons (Steimel et al 2013), and also functions in vulval development by regulating the epidermal growth factor receptor-Ras-extracellular signal-regulated kinase pathway (Grants et al 2016).…”

mentioning

confidence: 99%

cdc-25.4, aCaenorhabditis elegansOrtholog ofcdc25, Is Required for Male Mating Behavior

Kawasaki

Park

et al. 2016

G3 Genes|Genomes|Genetics

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Cell division cycle 25 (cdc25) is an evolutionarily conserved phosphatase that promotes cell cycle progression. Among the four cdc25 orthologs in Caenorhabditis elegans, we found that cdc-25.4 mutant males failed to produce outcrossed progeny. This was not caused by defects in sperm development, but by defects in male mating behavior. The cdc-25.4 mutant males showed various defects during male mating, including contact response, backing, turning, and vulva location. Aberrant turning behavior was the most prominent defect in the cdc-25.4 mutant males. We also found that cdc-25.4 is expressed in many neuronal cells throughout development. The turning defect in cdc-25.4 mutant males was recovered by cdc-25.4 transgenic expression in neuronal cells, suggesting that cdc-25.4 functions in neurons for male mating. However, the neuronal morphology of cdc-25.4 mutant males appeared to be normal, as examined with several neuronal markers. Also, RNAi depletion of wee-1.3, a C. elegans ortholog of Wee1/Myt1 kinase, failed to suppress the mating defects of cdc-25.4 mutant males. These findings suggest that, for successful male mating, cdc-25.4 does not target cell cycles that are required for neuronal differentiation and development. Rather, cdc-25.4 likely regulates noncanonical substrates in neuronal cells.

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The kinesin-3 family motor KLP-4 regulates anterograde trafficking of GLR-1 glutamate receptors in the ventral nerve cord ofCaenorhabditis elegans

Cited by 40 publications

References 82 publications

Palmitoylation of δ-catenin promotes kinesin-mediated membrane trafficking of Na _v 1.6 in sensory neurons to promote neuropathic pain

Palmitoylation of δ-catenin promotes kinesin-mediated membrane trafficking of Na _v 1.6 in sensory neurons to promote neuropathic pain

The DAF-7/TGF-β signaling pathway regulates abundance of the Caenorhabditis elegans glutamate receptor GLR-1

cdc-25.4, aCaenorhabditis elegansOrtholog ofcdc25, Is Required for Male Mating Behavior

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The kinesin-3 family motor KLP-4 regulates anterograde trafficking of GLR-1 glutamate receptors in the ventral nerve cord ofCaenorhabditis elegans

Cited by 40 publications

References 82 publications

Palmitoylation of δ-catenin promotes kinesin-mediated membrane trafficking of Na v 1.6 in sensory neurons to promote neuropathic pain

Palmitoylation of δ-catenin promotes kinesin-mediated membrane trafficking of Na v 1.6 in sensory neurons to promote neuropathic pain

The DAF-7/TGF-β signaling pathway regulates abundance of the Caenorhabditis elegans glutamate receptor GLR-1

cdc-25.4, aCaenorhabditis elegansOrtholog ofcdc25, Is Required for Male Mating Behavior

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Palmitoylation of δ-catenin promotes kinesin-mediated membrane trafficking of Na _v 1.6 in sensory neurons to promote neuropathic pain

Palmitoylation of δ-catenin promotes kinesin-mediated membrane trafficking of Na _v 1.6 in sensory neurons to promote neuropathic pain