Liu KK et al. (1995) Neuron "Sensory regulation of male mating behavior in Caenorhabditis elegans."

Liu KK, Sternberg PW

[Neuron, 1995]

C. elegans male mating behavior comprises a series of steps: response to contact with the hermaphrodite, backing along her body, turning around her head or tail, location of the vulva, insertion of the two copulatory spicules into the vulva, and sperm transfer. By ablation of male-specific copulatory structures and their associated neurons, we have identified sensory structures and neurons that participate in each of these steps: the sensory rays mediate response to contact and turning; the hook, the postcloacal sensilla and the spicules mediate vulva location; the spicules also mediate insertion and regulate sperm transfer. Generally, successful completion of each step places the male in a position to receive a cue for the next step in the pathway. However, the high degree of sensory regulation allows the male to execute some steps

Tokumitsu H et al. (1999) J Biol Chem "Substrate recognition by Ca2+/Calmodulin-dependent protein kinase kinase. Role of the arg-pro-rich insert domain."

Takahashi N, Yano S, Eto K, Muramatsu M, Tokumitsu H, Soderling TR

[J Biol Chem, 1999]

Mammalian Ca2+/CaM-dependent protein kinase kinase (CaM-KK) has been identified and cloned as an activator for two kinases, CaM kinase I (CaM-KI) and CaM kinase IV (CaM-KIV), and a recent report (Yano, S., Tokumitsu, H., and Soderling, T. R. (1998) Nature 396, 584-587) demonstrates that CaM-KK can also activate and phosphorylate protein kinase B (PKB). In this study, we identify a CaM-KK from Caenorhabditis elegans, and comparison of its sequence with the mammalian CaM-KK alpha and beta shows a unique Arg-Pro (RP)-rich insert in their catalytic domains relative to other protein kinases. Deletion of the RP-domain resulted in complete loss of CaM-KIV activation activity and physical interaction of CaM-KK with glutathione S-transferase-CaM-KIV (T196A). However, CaM-KK autophosphorylation and phosphorylation of a synthetic peptide substrate were normal in the RP-domain mutant. Site-directed mutagenesis of three conserved Arg in the RP- domain of CaM-KK confirmed that these positive charges are important for CaM-KIV activation. The RP- domain deletion mutant also failed to fully activate and phosphorylate CaM-KI, but this mutant was indistinguishable from wild-type CaM-KK for the phosphorylation and activation of PKB. These results indicate that the RP-domain in CaM-KK is critical for recognition of downstream CaM-kinases but not for its catalytic activity (i.e. autophosphorylation) and PKB activation.

Eto K et al. (1999) J Biol Chem "Ca(2+)/Calmodulin-dependent protein kinase cascade in Caenorhabditis elegans. Implication in transcriptional activation."

Kimura Y, Eto K, Tokumitsu H, Arai K, Takahashi N, Muramatsu M, Masuho Y

[J Biol Chem, 1999]

We have recently demonstrated that Caenorhabditis elegans Ca(2+)/calmodulin-dependent protein kinase kinase (CeCaM-KK) can activate mammalian CaM-kinase IV in vitro (Tokumitsu, H., Takahashi, N., Eto, K., Yano, S., Soderling, T.R., and Muramatsu, M. (1999) J. Biol. Chem. 274, 15803-15810). In the present study, we have identified and cloned a target CaM-kinase for CaM-KK in C. elegans, CeCaM-kinase I (CeCaM-KI), which has approximately 60% identity to mammalian CaM-KI. CeCaM-KI has 348 amino acid residues with an apparent molecular mass of 40 kDa, which is activated by CeCaM-KK through phosphorylation of Thr(179) in a Ca(2+)/CaM-dependent manner, resulting in a 30-fold decrease in the K(m) of CeCaM-KI for its peptide substrate. Unlike mammalian CaM-KI, CeCaM-KI is mainly localized in the nucleus of transfected cells because the NH(2)-terminal six residues ((2)PLFKRR(7)) contain a functional nuclear localization signal. We have also demonstrated that CeCaM-KK and CeCaM-KI reconstituted a signaling pathway that mediates Ca(2+)-dependent phosphorylation of cAMP response element-binding protein (CREB) and CRE-dependent transcriptional activation in transfected cells, consistent with nuclear localization of CeCaM-KI. These results suggest that the CaM-KK/CaM-KI cascade is conserved in C. elegans and is functionally operated both in vitro and in intact cells, and it may be involved in Ca(2+)-dependent nuclear events such as transcriptional activation through phosphorylation of CREB.

Kaplan HS et al. (2018) Neuron "Sensorimotor Integration for Decision Making: How the Worm Steers."

Zimmer M, Kaplan HS

[Neuron, 2018]

Animals' movements actively shape their perception and subsequent decision making. In this issue of Neuron, Liu etal. (2018) show how C.elegans nematodes steer toward an odorant: a dedicated interneuron class integrates oscillatory olfactory signals, generated by head swings, with corollary discharge motor signals.

Ali L et al. (2020) J Cell Biol "Mitochondrial translation, dynamics, and lysosomes combine to extend lifespan."

Ali L, Haynes CM

[J Cell Biol, 2020]

In this issue, Liu et al. (2019. J. Cell. Biol.https://doi.org/10.1083/jcb.201907067) find that the inhibition of mitochondrial ribosomes in combination with impaired mitochondrial fission or fusion increases C. elegans lifespan by activating the transcription factor HLH-30, which promotes lysosomal biogenesis.

Rahmani, Shapour et al. (2021) MicroPubl Biol

Tuck, Simon, Rahmani, Shapour

[MicroPubl Biol, 2021]

C. elegans males that have come into close proximity of hermaphrodites initiate copulatory behavior comprising at least five different steps termed response, turning, location of vulva, spicule insertion and sperm transfer (Loer and Kenyon 1993, Liu and Sternberg 1995, Chute and Srinivasan 2014). Mutations specifically affecting different steps have been isolated and characterized (Barr and Sternberg 1999, Hajdu-Cronin et al. 2017, Liu et al. 2017). However, our understanding of the molecular mechanisms acting in the neurons controlling copulation is far from complete. During the response step, males that have sensed the presence of a hermaphrodite move backwards in such a way that the males tail fan glides along the surface of the hermaphrodite until the tail reaches the vulva (or head or tail) (Loer and Kenyon 1993, Liu and Sternberg 1995, Sherlekar and Lints 2014). Response behavior is regulated by ciliated neurons in the tail whose dendrites lie in sensory rays within the fan (Liu and Sternberg 1995). If a male reaches the end of the hermaphrodite without having found the vulva, it executes a turn during which the tail bends tightly ventrally so that contact is established between the ventral surface of the fan and the other side of the intended mate (Loer and Kenyon 1993, Liu and Sternberg 1995). The ability to execute turns efficiently is dependent upon serotonergic neurons in the posterior ventral nerve cord (the CP neurons) and on their ability to produce serotonin (Loer and Kenyon 1993, Carnell et al. 2005). Serotonin stimulates the diagonal muscles in the tail to induce curling ventrally by stimulating a serotonin receptor, SER-1 (Loer and Kenyon 1993, Carnell et al. 2005). However, how serotonin affects diagonal muscles and ventral turning is not fully understood.

Arena JP et al. (1991) Mol Pharmacol "Avermectin-sensitive chloride currents induced by Caenorhabditis elegans RNA in Xenopus oocytes."

Arena JP, Paress PS, Cully DF, Liu KK

[Mol Pharmacol, 1991]

Avermectins are a family of potent broad-spectrum anthelmintic compounds, which bind with high affinity to membranes isolated from the free-living nematode Caenorhabditis elegans. Binding of avermectins is thought to modulate chloride channel activity, but the exact mechanism for anthelmintic activity remains to be determined. In this report, the properties of an avermectin-sensitive membrane current were evaluated in Xenopus laevis oocytes that were injected with poly(A)+ RNA from C. elegans. In such oocytes, avermectins increased inward membrane current at a holding potential of -80 mV. An avermectin analog without anthelmintic activity had no effect. Half-maximal activation of current was observed with 90 nM avermectin. The reversal potential for avermectin-sensitive current was -19.3 +/- 1.9 mV, and it shifted with external chloride, as expected for a chloride current. Avermectin increased membrane current in C. elegans-injected oocytes that were also injected with the Ca2+ chelator ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. The response to avermectin was greatest in the 1.0-2.5-kilobase class of size-fractionated C. elegans poly(A)+ RNA. Oocytes that responded to avermectin were insensitive to gamma-aminobutyric acid and the avermectin-induced current was blocked by picrotoxin.

Etter A et al. (1996) J Biol Chem "An amino acid substitution in the pore region of a glutamate-gated chloride channel enables the coupling of ligand binding to channel gating."

Cully DF, Arena JP, Liu KK, Etter A, Schaeffer JM

[J Biol Chem, 1996]

Many of the subunits of ligand-gated ion channels respond poorly, if at all, when expressed as homomeric channels in Xenopus oocytes. This lack of a ligand response has been thought to result from poor surface expression, poor assembly, or lack of an agonist binding domain. The Caenorhabditis elegans glutamate-gated chloride channel subunit GluClbeta responds to glutamate as a homomeric channel while the GluClalpha subunit is insensitive. A chimera between GluClalpha and GluClbeta was used to suggest that major determinants for glutamate binding are present on the GluClalpha N terminus. Amino acid substitutions in the presumed pore of GluClalpha conferred direct glutamate gating indicating that GluClalpha is deficient in coupling of ligand binding to channel gating. Heteromeric channels of GluClalpha+beta may differ from the prototypic muscle nicotinic acetylcholine receptor in that they have the potential to bind ligand to all of the subunits forming the channel.

Arena JP et al. (1992) Brain Res Mol Brain Res "Expression of a glutamate-activated chloride current in Xenopus oocytes injected with Caenorhabditis elegans RNA: evidence for modulation by avermectin."

Schaeffer JM, Arena JP, Paress PS, Liu KK, Cully DF

[Brain Res Mol Brain Res, 1992]

Membrane currents were recorded from Xenopus laevis oocytes injected with C. elegans poly(A)+ RNA. In such oocytes glutamate activated an inward membrane current that desensitized in the continued presence of glutamate. Glutamate-receptor agonists quisqualate, kainate, and N-methyl-D-aspartate were inactive. The reversal potential of the glutamate-sensitive current was -22 mV, and exhibited a strong dependence on external chloride with a 48 mV change for a 10-fold change in chloride. The chloride channel blockers flufenamate and picrotoxin inhibited the glutamate-sensitive current. Ibotenate, a structural analog of glutamate, also activated a picrotoxin-sensitive chloride current. Ibotenate was inactive when current was partially desensitized with glutamate, and the responses to low concentrations of glutamate and ibotenate were additive. The anthelmintic/insecticide compound avermectin directly activated the glutamate-sensitive current. In addition, avermectin increased the response to submaximal concentrations of glutamate, shifted the glutamate concentration-response curve to lower concentrations, and slowed the desensitization of glutamate-sensitive current. We propose that the glutamate-sensitive chloride current and the avermectin-sensitive chloride current are mediated via the same channel.

Liu J et al. (1996) Science "Interaction between a putative mechanosensory membrane channel and a collagen."

Schrank B, Waterston RH, Liu J

[Science, 1996]

The degenerin family of proteins in Caenorhabditis elegans is homologous to subunits of the mammalian amiloride-sensitive epithelial sodium channels. Mutations in nematode degenerins cause cell death, probably because of defects in channel function. Genetic evidence was obtained that the unc-105 gene product represents a degenerin homolog affecting C. elegans muscles and that this putative channel interacts with type IV collagen in the extracellular matrix underlying the muscle cell. This interaction may serve as a mechanism of stretch-activated muscle contraction, and this system could provide a molecular model for the activation of mechanosensitive ion channels.AD - Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.FAU - Liu, JAU - Liu JFAU - Schrank, BAU - Schrank BFAU - Waterston, R HAU - Waterston RHLA - engSI - GENBANK/J04694SI - GENBANK/M23704SI - GENBANK/M67507SI - GENBANK/U07224SI - GENBANK/U07888SI - GENBANK/U22327SI - GENBANK/X56979SI - GENBANK/X76730SI - GENBANK/Y00706ID - GM23883/GM/NIGMSPT - Journal ArticleCY - UNITED STATESTA - ScienceJID - 0404511RN - 0 (Helminth Proteins)RN - 0 (Sodium Channels)RN - 0 (Unc-105 protein)RN - 9007-34-5 (Collagen)SB - IMSB - S