Chang SY et al. (2017) J Microbiol Biotechnol "Erratum to: Genome Characteristics of Lactobacillus fermentum Strain JDFM216 for Application as Probiotic Bacteria."

Lee HK, Heo J, Chang SY, Jeong DY, Oh S, Jo SH, Kim Y, Park MR, Song MH, Kim JN

[J Microbiol Biotechnol, 2017]

This erratum is being published to correct the 1st author's name of above manuscript by Jang et al. that was published in Journal of Microbiology and Biotechnology (2017, 27: 1266-1271). The 1st author name(Sung Yong Jang) should appear as 'Sung Yong Chang'.

Han H-P et al. (1992) Worm Breeder's Gazette "Expression and Localization of the cha-1 and unc-17 Gene Products"

Rand JB, Duerr JS, Han H-P

[Worm Breeder's Gazette, 1992]

EXPRESSION AND LOCALIZATION OF THE cha-l AND unc-17 GENE PRODUCTS He-ping Han, Janet Duerr, and Jim Rand, Oklahoma Medlcal Research Foundation, Oklahoma Clty, OK 73104

Tae Hoon Lee et al. (2008) "Physiological properties of C. elegans are affected by DIC-1 that controls mitochondrial cristae morphology"

Hyeon-Sook Koo, Tae Hoon Lee, Sung Sik Han, Ji Young Mun

[2008]

"In our previous study we suggested, C. elegans DIC-1 was localized in the inner membrane of mitochondria at cristae and its knockdown resulted in the formation of mitochondria containing numerous internal vesicles. When DIC-1 was overexpressed under a heat shock promoter in a transgenic C. elegans line, the number of cristae per cross-sectional area of mitochondria was greatly increased, supporting the role of DIC-1 in cristae formation. The oxygen consumption rate of the dic-1 knockdown strain was similar to that of control worms, but interestingly, the dic-1 overexpression line showed an increased oxygen consumption rate. The ATP content of the dic-1 knockdown strain was decreased compare to that of control worms, but dic-1 overexpressed line showed an increased ATP content. One peculiar characteristic of the worms after the knockdown was a greatly increased resistance of the worms to paraquat, which is usually observed in worms with a decreased mitochondrial activity. Nevertheless, the intracellular level of H2O2-related reactive oxygen species was slightly increased after the dic-1 knockdown, opposing the possibility that the increased resistance to paraquat was due to a low ROS level. By contrast, the dic-1 overexpression line showed hypersensitivity to paraquat. In summary, C. elegans DIC-1 plays a critical role in the formation of normal morphology of mitochondrial cristae/inner membrane and affects physiological properties of the worms, such as respiration rate, ATP contents, intracellular ROS level, and sensitivity to exogenous oxidative stress. This work was supported by Seoul Development Institute."

Gruber J et al. (2017) Cell "Microbiome and Longevity: Gut Microbes Send Signals to Host Mitochondria."

Kennedy BK, Gruber J

[Cell, 2017]

The microbiome has emerged as a major determinant of the functioning of host organisms, affecting both health and disease. Here, Han etal. use the workhorse of aging research, C.elegans, to identify specific mechanisms by which gut bacteria influence mitochondrial dynamics and aging, a first steptoward analogous manipulations to modulate human aging.

Grubbs JJ et al. (2020) PLoS Biol "A salt-induced kinase is required for the metabolic regulation of sleep."

Lopes LE, Raizen DM, Grubbs JJ, van der Linden AM

[PLoS Biol, 2020]

Many lines of evidence point to links between sleep regulation and energy homeostasis, but mechanisms underlying these connections are unknown. During Caenorhabditis elegans sleep, energetic stores are allocated to nonneural tasks with a resultant drop in the overall fat stores and energy charge. Mutants lacking KIN-29, the C. elegans homolog of a mammalian Salt-Inducible Kinase (SIK) that signals sleep pressure, have low ATP levels despite high-fat stores, indicating a defective response to cellular energy deficits. Liberating energy stores corrects adiposity and sleep defects of kin-29 mutants. kin-29 sleep and energy homeostasis roles map to a set of sensory neurons that act upstream of fat regulation as well as of central sleep-controlling neurons, suggesting hierarchical somatic/neural interactions regulating sleep and energy homeostasis. Genetic interaction between kin-29 and the histone deacetylase hda-4 coupled with subcellular localization studies indicate that KIN-29 acts in the nucleus to regulate sleep. We propose that KIN-29/SIK acts in nuclei of sensory neuroendocrine cells to transduce low cellular energy charge into the mobilization of energy stores, which in turn promotes sleep.

Greenwald IS et al. (1990) Cell "Cell fates in C. elegans: in medias ras."

Greenwald IS, Broach JR

[Cell, 1990]

ras proteins play a central role in controlling cell proliferation in a variety of organisms and also appear to mediate specific developmental processes in certain cells. Nonetheless, how ras protein activity is regulated and how ras protein activation yields its biological effect have not been clearly defined in any metazoan. Now, Han and Sternberg (1990a) have found that a ras protein is encoded by the C. elegans let-60 gene. Since powerful classical and molecular genetic methods are available for C. elegans, this finding offers great promise for identifying components of the ras pathway and defining the nature of their interactions in this organism. In addition, the extensive literature on the biochemistry and genetics of ras function in other organisms should greatly facilitate translating genetic analysis of let-60 (Beitel et al., 1990; Han and Sternberg, 1990b) into detailed molecular models of cell fate determination.

Yeh Chan-Hsien et al. (2007) International Worm Meeting "Screen for TLK-1-interacting proteins."

Yi-Chun Wu, Yeh Chan-Hsien, I-Ju Lee

[International Worm Meeting, 2007]

Tousled-like kinases (TLKs) form a conserved serine/threonine kinase family in multi-cellular organisms and have been implicated in transcription, DNA replication and repair and chromosome assembly and segregation. The tlk-1(RNAi) mutants exhibited defects in chromosome condensation and segregation. Previous studies of C. elegans TLK-1 indicates that tlk-1 may act in chromosome assembly by phosphorylating Asf-1 (anti-silencing function protein) and contribute to chromosome segregation as a substrate and activator of the Aurora B kinase AIR-2 (Han et al, 2005). To identify more TLK-1-interacting proteins, we performed a yeast-two hybrid screen. In the screen we isolated DLC-1 (Dynein light chain). DLC-1 is localized to spindle fiber during mitosis and this localization pattern is disrupted in tlk-1(RNAi) embryos. We are currently performing experiments to verify the interaction between DLC-1 and TLK-1 in vivo and investigating if TLK-1 may phosphorylate DLC-1. Reference Han, Z., Riefler, G.M., Saam, J.R., Mango, S.E., and Schumacher, J.M. (2005) Curr. Biol., 15, 894-904.

Sung Min Han et al. (2006) East Asia C. elegans Meeting "Deleted in cancer 1 (DICE1) is an essential protein controlling the topology of the inner mitochondrial membrane in C. elegans"

Se-Jin Lee, Michael O. Hengartner, Tae Hoon Lee, Ekaterini Kritikou, Hyeon-Sook Koo, Ji Young Mun, Sung Min Han, Moon Jeong Kim, Sung Sik Han

[East Asia C. elegans Meeting, 2006]

DICE1 (deleted in cancer 1), first identified in human lung carcinoma cell lines, is a candidate tumor suppressor, but the details of its activity remain largely unknown. We have found that RNA interference of its C. elegans homolog (DIC-1) produced inviable embryos with increased apoptosis, cavities in cells and abnormal morphogenesis. In the dic-1(RNAi)germ line, ced-3-dependent apoptosis increased, and cell cavities appeared at the late-pachytene/oogenic stage, leading to defective oogenesis. Immunofluorescence microscopy of DIC-1 revealed its ubiquitous expression in the form of cytoplasmic foci, and cryoelectron microscopy narrowed down the location of the foci to the inner membrane of mitochondria. After dic-1 RNAi, mitochondria had an irregular morphology and contained numerous internal vesicles. Homozygous embryos from a heterozygous dic-1 mother arrested at the L3 larval stage, in agreement with the essential role of DIC-1 in mitochondria. In summary, C. elegans DIC-1 plays a crucial role in the formation of normal morphology of the mitochondrial cristae/inner membrane. Our results suggest that human DICE1 may have several functions in multiple intracellular locations.

Kim SH et al. (2019) Anim Cells Syst (Seoul) "Calcineurin tax-6 regulates male ray development and counteracts with kin-29 kinase in Caenorhabditis elegans."

Lee SK, Jung H, Kim SH, Ahnn J

[Anim Cells Syst (Seoul), 2019]

Phosphorylation is one of the critical protein modifications, which can lead to changing the activity of the proteins and regulating a variety of biological processes. Therefore, it is essential to properly maintain the phosphorylation level on proteins by balancing the activity of kinases and phosphatases. In this study, we report that calcineurin, a serine/threonine phosphatase, counteracts with a salt inducible kinase (SIK) to control male tail development in <i>Caenorhabditis elegans</i>. The counteracting regulation is cell lineage-dependent; the number of defective rays from T lineage in animals lacking calcineurin <i>tax-6</i> is decreased by knock-down of SIK <i>kin-29</i>. This result is in contrast with the knock-down of bone marrow protein (BMP) receptor kinase <i>sma-6</i>, which slightly aggravates the T lineage defect. Also, <i>sma-6</i> knock-down results in modest defect in ray 1 of V5 lineage in the absence of <i>tax-6</i> activity. Finally, knock-down of a tyrosine phosphatase <i>cdc-25.3</i> does not affect the defective ray phenotype of calcineurin <i>tax-6 loss-of-function(lf)</i> mutants. Altogether, these results suggest that balanced phosphorylation mediated by <i>tax-6</i> and <i>kin-29</i> is required for proper development of T lineage rays, and <i>tax-6</i> and <i>sma-6</i> may function in a parallel pathway in the developmental process of V5 lineage ray 1. This study emphasizes the elaborated developmental process of male ray formation, in which carefully coordinated expression of various genes is essential.

Grubbs, J. J. et al. (2019) International Worm Meeting "A salt-induced kinase (SIK) is required for the metabolic regulation of sleep."

van der Linden, A. M., Lopes, L. E., Raizen, D. M., Grubbs, J. J.

[International Worm Meeting, 2019]

Many lines of evidence point to links between sleep regulation and energy homeostasis, but mechanisms underlying these connections are unclear. C. elegans sleeps during development (developmentally timed sleep or DTS), during starvation, and following cellular stress (stress-induced sleep or SIS). We find that during DTS, when a cuticle is secreted, and during SIS, when cellular homeostasis is restored, ATP levels and body fat stores are reduced, suggesting that during sleep, energetic stores are allocated to non-neural tasks. Loss of kin-29, which encodes a homologue of a mammalian Salt-Inducible Kinase (SIK) that signal sleep pressure, results in low ATP levels despite high fat stores, indicating a defective response to cellular energy deficits. Liberating energy stores by overexpressing the triglyceride lipase ATGL-1 corrects adiposity and sleep defects of kin-29 mutants. We performed pharmacological experiments that suggest that sleep is promoted by beta-oxidation of fatty acids. kin-29 sleep and energy homeostasis roles map to a small number of sensory neurons, including ASJ and ASK, that act upstream of fat regulation as well as of the central sleep-controlling neurons, ALA and RIS, suggesting hierarchical somatic/neural interactions regulating sleep and energy homeostasis. Genetic interaction between kin-29 and the histone deacetylase hda-4 coupled with subcellular localization studies indicate that KIN-29 acts in the nucleus to regulate sleep. A KIN-29 protein with serine 517 mutated to Alanine was unable to move to the nucleus during sleep and was defective for sleep. We propose that KIN-29/SIK acts in nuclei of sensory neuroendocrine cells to transduce low cellular energy charge into the mobilization of energy stores, which in turn promotes sleep. SIKs are therefore key nodes integrating sleep and energy homeostasis.