Hyeon‐Sook Koo

Calcineurin is a Ca(2+)-calmodulin-dependent serine/threonine protein phosphatase that has been implicated in various signaling pathways. Here we report the identification and characterization of calcineurin genes in Caenorhabditis elegans (cna-1 and cnb-1), which share high homology with Drosophila and mammalian calcineurin genes. C. elegans calcineurin binds calcium and functions as a heterodimeric protein phosphatase establishing its biochemical conservation in the nematode. Calcineurin is expressed in hypodermal seam cells, body-wall muscle, vulva muscle, neuronal cells, and in sperm and the spermatheca. cnb-1 mutants showed pleiotropic defects including lethargic movement and delayed egg-laying. Interestingly, these characteristic defects resembled phenotypes observed in gain-of-function mutants of unc-43/Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) and goa-1/G(o)-protein alpha-subunit. Double mutants of cnb-1 and unc-43(gf) displayed an apparent synergistic severity of movement and egg-laying defects, suggesting that calcineurin may have an antagonistic role in CaMKII-regulated phosphorylation signaling pathways in C. elegans.

AAK-2 is one of two alpha isoforms of the AMP-activated protein kinase in Caenorhabditis elegans and is involved in life span maintenance, stress responses, and germ cell cycle arrest upon dauer entry. We found that AAK-2 was phosphorylated at threonine 243 in response to paraquat treatment and that this phosphorylation depends on PAR-4, the C. elegans LKB1 homologue. Both aak-2 mutation and par-4 knockdown increased the sensitivity of C. elegans worms to paraquat, and the double deficiency did not further increase sensitivity, indicating that aak-2 and par-4 act in a linear pathway. Both mutations also slowed body bending during locomotion and failed to reduce head oscillation in response to anterior touch. Consistent with this abnormal motility and behavioral response, expression of the AAK-2::green fluorescent protein fusion protein was observed in the ventral cord, some neurons, body wall muscle, pharynx, vulva, somatic gonad, and excretory cell. Our study suggests that AMPK can influence the behavior of C. elegans worms in addition to its well known function in metabolic control.

BACKGROUND: High-resolution manometry (HRM) based on spatiotemporal plots is increasingly being used. The aim this study was to evaluate, for the first time, the influence of gender, with adjustment for age, body mass index (BMI), and vaginal delivery, on anorectal functions in asymptomatic adults. METHODS: Fifty-four asymptomatic healthy subjects (M : F = 27 : 27; age = 20-67 years) who were matched by age and gender were enrolled prospectively. We evaluated anorectal pressures, rectal sensation using a HRM probe, and balloon expulsion time. Multivariate linear regression analysis was performed to identify the independent effects of each factor. KEY RESULTS: Anal resting pressure (median [IQR]; 32 [18] vs 46 [17] mmHg, p < 0.001), anal squeeze pressure (75 [28] vs 178 [72] mmHg, p < 0.001), rectal pressure (33 [16] vs 53 [46] mmHg, p = 0.009) and anal pressure (16 [17] vs 30 [36] mmHg, p = 0.019) during simulated evacuation with rectal distention, and the threshold for the desire to defecate (60 [20] vs 80 [60] mL, p = 0.020) were significantly lower in women than in men. BMI was positively correlated with anal resting pressure (95% CI: 0.598-2.947) and negatively correlated with the threshold for first sensation (95% CI: -0.099 to -0.015). Vaginal delivery did not affect any of the anorectal HRM parameters. CONCLUSIONS & INFERENCES: HRM parameters may be associated with gender and BMI. Therefore, gender and BMI should be taken into consideration when interpreting HRM results.