Endogenous chondroitin extends the lifespan and healthspan in C. elegans.

Chondroitin, a class of glycosaminoglycan polysaccharides, is found as proteoglycans in the extracellular matrix, plays a crucial role in tissue morphogenesis during development and axonal regeneration. Ingestion of chondroitin prolongs the lifespan of C. elegans. However, the roles of endogenous chondroitin in regulating lifespan and healthspan mostly remain to be investigated. Here, we demonstrate that a gain-of-function mutation in MIG-22, the chondroitin polymerizing factor (ChPF), results in elevated chondroitin levels and a significant extension of both the lifespan and healthspan in C. elegans. Importantly, the remarkable longevity observed in mig-22(gf) mutants is dependent on SQV-5/chondroitin synthase (ChSy), highlighting the pivotal role of chondroitin in controlling both lifespan and healthspan. Additionally, the mig-22(gf) mutation effectively suppresses the reduced healthspan associated with the loss of MIG-17/ADAMTS metalloprotease, a crucial for factor in basement membrane (BM) remodeling. Our findings suggest that chondroitin functions in the control of healthspan downstream of MIG-17, while regulating lifespan through a pathway independent of MIG-17.

Strongly alkaline pH avoidance mediated by ASH sensory neurons in C. elegans.

High pH is a noxious stimulus to animals, and their ability to avoid dangerously alkaline pH is critical for survival. However, the means by which they sense high pH has not been determined. The nematode Caenorhabditis elegans (C. elegans) avoids environmental pH above 10.5. In contrast, C. elegans mutants with structurally, developmentally, and/or functionally abnormal sensory cilia fail to avoid high pH, suggesting that sensory neurons in the cilia participate in sensing. Genetic rescue of the mutants indicates that ASH polymodal sensory neurons play a vital role in the process. Consistently, specific laser ablation of ASH neurons made animals insensitive to high pH. Furthermore, avoidance assays of other mutants also indicated that transient receptor potential vanilloid type (TRPV) ion channels encoded by osm-9 and ocr-2 are involved in sensing. Indeed, genetic rescue of osm-9 mutants by specifically expressing OSM-9 in ASH showed that TRPV channels play an essential role in sensing of high pH. Ca(2+) imaging in vivo also revealed that ASH neurons were activated by high pH stimulation, but ASH of osm-9 or ocr-2 mutants were not. These results demonstrate that in C. elegans, high pH is sensed by ASH nociceptors through opening of OSM-9/OCR-2 TRPV channels.

A G-protein α subunit, GOA-1, plays a role in C. elegans avoidance behavior of strongly alkaline pH.

The ability of animals to avoid strongly alkaline pH is critical for survival. However, the means by which they sense high pH has not been determined. We have previously found that the nematode Caenorhabditis elegans (C. elegans) avoids environmental pH above 10.5. Detection involves ASH nociceptive neurons as the major sensors. Upon stimulation, transient receptor potential vanilloid-type (TRPV) ion channels encoded by osm-9 and ocr-2 play an essential role in Ca(2+) entry into ASH. Here we report that C. elegans mutants deficient in a G-protein α subunit, GOA-1, failed to avoid strongly alkaline pH with normal Ca(2+) influx into ASH. These results suggest that GOA-1 regulates signal transmission downstream of Ca(2+) influx through OSM-9/OCR-2 TRPV channels in ASH.

Memory in Caenorhabditis elegans is mediated by NMDA-type ionotropic glutamate receptors.

Learning and memory are essential processes of both vertebrate and invertebrate nervous systems that allow animals to survive and reproduce. The neurotransmitter glutamate signals via ionotropic glutamate receptors (iGluRs) that have been linked to learning and memory formation; however, the signaling pathways that contribute to these behaviors are still not well understood. We therefore undertook a genetic and electrophysiological analysis of learning and memory in the nematode Caenorhabditis elegans. Here, we show that two genes, nmr-1 and nmr-2, are predicted to encode the subunits of an NMDA-type (NMDAR) iGluR that is necessary for memory retention in C. elegans. We cloned nmr-2, generated a deletion mutation in the gene, and showed that like nmr-1, nmr-2 is required for in vivo NMDA-gated currents. Using an associative-learning paradigm that pairs starvation with the attractant NaCl, we also showed that the memory of a learned avoidance response is dependent on NMR-1 and NMR-2 and that expression of NMDARs in a single pair of interneurons is sufficient for normal memory. Our results provide new insights into the molecular and cellular mechanisms underlying the memory of a learned event.

Role of Caenorhabditis elegans protein phosphatase type 1, CeGLC-7 beta, in metaphase to anaphase transition during embryonic development.

In Caenorhabditis elegans embryogenesis, phosphorylation events are critical to chromosomal changes. To investigate the dephosphorylation of chromosome behavior, we cloned and characterized the cDNA that encodes C. elegans protein phosphatase type 1 (CeGLC-7 beta), which is composed of 333 amino acids. CeGLC-7 beta possesses a highly conserved amino acid sequence with mammalian and Drosophila protein phosphatase 1. Here, we report on the contribution of CeGLC-7 beta to the dephosphorylation of histone H3 at anaphase. At the embryonic stage, CeGLC-7 beta is associated with the nuclear membrane and chromosomes. The deletion of the Ceglc-7 beta gene and a microinjection of double-stranded RNA produce a disorganized embryogenesis. The Ceglc-7 beta gene mutation causes an abnormal accumulation of phosphorylated histone H3 and delays the mitotic process after anaphase. We propose that CeGLC-7 beta is involved in chromosome dynamics including histone H3 dephosphorylation.

A mutant exhibiting abnormal habituation behavior in Caenorhabditis elegans.

The acquisition and retention of information by the nervous system are major processes of learning. Habituation is a simple learning process that occurs during repeated exposure to harmless stimuli. C. elegans is habituated when repeatedly given mechanical stimuli and recover from the habituation when the stimuli are stopped. A habituation abnormal mutant was isolated and assigned to a new gene hab-1 whose mutation causes slow habituation. The hab-1 mutant phenotype is remarkable at short time interval stimuli. However, hab-1 mutant worms show normal dishabituation. Ablations of neurons constituting the neural circuit for mechanical reflexes did not abolish abnormalities caused by the hab-1 mutation.