Eve A (2021) Development "An interview with Swathi Arur."

Eve A

[Development, 2021]

Swathi Arur is an Associate Professor for the Department of Genetics at the MD Anderson Cancer Center, USA, where she uses multidisciplinary approaches to understand female germline development and fertility. She has received numerous accolades, including the MD Anderson Distinguished Research Faculty Mentor Award in 2017. In 2020, she was elected to the American Association for the Advancement of Science (AAAS). Swathi joined the team at Development as an Academic Editor in 2020, and we met with her over Zoom to hear more about her life, her career and her love for <i>C. elegans</i>.

Dixon JR (2019) Dev Cell "TADs for Life: Chromatin Domain Organization Regulates Lifespan in C.elegans."

Dixon JR

[Dev Cell, 2019]

In this issue of Developmental Cell, Anderson etal. (2019) show that chromatin domain structure on the X chromosome in C.elegans is dispensable for dosage compensation but regulates longevity and thermotolerance. This study sheds light on the mechanisms of domain formation in C.elegans and how these features affect physiology.

Antol, Weronika et al. (2022) MicroPubl Biol

Sychta, Karolina, Prokop, Zofia M., Antol, Weronika, Palka, Joanna K., Dudek, Katarzyna

[MicroPubl Biol, 2022]

Caenorhabditis elegans is a model species, increasingly used in experimental evolution studies to investigate such major topics as: maintenance of genetic variation, host-pathogen interaction and coevolution, mutations, life history, evolution of reproductive systems, sexual selection (Gray and Cutter, 2014; Teotnio, Estes, Phillips, and Baer, 2017). Its reproductive system in the wild, known as androdioecy, involves mostly self-fertilization of hermaphrodites and occasionally outcrossing with males, which are generally rare (Stewart and Phillips, 2002). This system can be experimentally changed to dioecy, i.e., obligatory outcrossing, through genetic manipulations (see Table I in Anderson, Morran, and Phillips, 2010; Gray and Cutter, 2014).

Kisiel MJ et al. (1969) Nematologica "Influence of a growth factor from bacteria on the morphology of C. briggsae."

Nelson B, Zuckerman BM, Kisiel MJ

[Nematologica, 1969]

Several investigators have reported that nutritional or environmental factors induce morphological variations in the "so-called' bacteriophagous nematodes. For example, Nigon & Dougherty described a morphological mutant of the free-living, self-fertilizing, hermaphroditic nematode Rhabditis (Caenorhabditis) briggsae that ensued following heat-treatment of progeny cultured on bacteria. Also Anderson reported that certain diagnostic features of an Acrobeloides sp., specifically the shape of the labial probolae and tail, varied significantly when the nematodes were grown on bacterial cultures as compared to those grown in soil. The current paper describes a consistent morphological variation in Caenorhabditis briggsae grown axenically on a meridic medium containing a growth factor from a bacterium as compared with nematodes reared on a growth factor from liver extract.

Anderson ARA et al. (1997) Fundamental and Applied Nematology "Nematode movement along a chemical gradient in a structurally heterogeneous environment. 2. Theory."

Young IM, Sleeman BD, Anderson ARA, Griffiths BS

[Fundamental and Applied Nematology, 1997]

The effects of structural heterogeneity on both chemical diffusion and nematode movement are examined with the development of a theoretical model. The model considers three factors affecting nematode movement: soil structure, nematode foraging strategy and chemotaxis. Using a continuous model, we develop a discrete system which allows nematode trails to be simulated in any of the four experimental conditions given by Anderson et al (1997). We show that structural heterogeneity causes mixed levels of attractant concentration over small areas as well as "fingering" of the attractant. Soil structural heterogeneity also restricts the foraging strategy of the nematode which then becomes a strategy to avoid structural "traps". The effect of localised increases in structural density is shown to increase significantly "fingering" of the attractant.

Ou G et al. (2007) Mol Biol Cell "Sensory ciliogenesis in Caenorhabditis elegans: assignment of IFT components into distinct modules based on transport and phenotypic profiles."

Koga M, Scholey JM, Leroux MR, Schafer JC, Ou G, Ohshima Y, Li C, Murayama T, Blacque OE, Yoder BK

[Mol Biol Cell, 2007]

Monitoring Editor: Erika Holzbaur Sensory cilium biogenesis within C. elegans neurons depends upon the kinesin-2-dependent intraflagellar transport (IFT) of ciliary precursors associated with IFT particles to the axoneme tip. Here we analyzed the molecular organization of the IFT machinery by comparing the in vivo transport and phenotypic profiles of multiple proteins involved in IFT and ciliogenesis. Based on their motility in WT and bbs (Bardet-Biedl syndrome) mutants, IFT-proteins were classified into groups with similar transport profiles which we refer to as "modules". We also analyzed the distribution of fluorescent IFT-particles in multiple known ciliary mutants and 49 new ciliary mutants. Most of the latter mutants were snip-SNP mapped and one, namely dyf-14(ks69), was cloned and found to encode a conserved protein essential for ciliogenesis. The products of these ciliogenesis genes could also be assigned to the aforementioned set of modules, or to specific aspects of IFT, based on their ciliary mutant phenotypes. While binding assays would be required to confirm direct physical interactions, the results are consistent with the hypothesis that the C. elegans IFT machinery has a modular design, consisting of modules IFT-subcomplex A, IFT-subcomplex B, a BBS protein complex, in addition to motor and cargo modules, with each module contributing to distinct functional aspects of IFT or ciliogenesis.

Efimenko E et al. (2006) Mol Biol Cell "Caenorhabditis elegans DYF-2, an orthologue of human WDR19, is a component of the intraflagellar transport machinery in sensory cilia."

Swoboda P, Efimenko E, Haycraft CJ, Yoder BK, Ou G, Blacque OE, Leroux MR, Scholey JM

[Mol Biol Cell, 2006]

Monitoring Editor: Erika Holzbaur The intraflagellar transport (IFT) machinery required to build functional cilia consists of a multisubunit complex whose molecular composition, organization and function is poorly understood. Here, we describe a novel WD repeat (WDR) containing IFT protein from C. elegans, DYF-2, that plays a critical role in maintaining the structural and functional integrity of the IFT machinery. We determined the identity of the dyf-2 gene by transgenic rescue of mutant phenotypes and by sequencing of mutant alleles. Loss of DYF-2 function selectively affects the assembly and motility of different IFT components and leads to defects in cilia structure and chemosensation in the nematode. Based on these observations, and the analysis of DYF-2 movement in a Bardet-Biedl syndrome mutant with partially disrupted IFT particles, we conclude that DYF-2 can associate with IFT particle complex B. At the same time, mutations in dyf-2 can interfere with the function of complex A components, suggesting an important role of this protein in the assembly of the IFT particle as a whole. Importantly, the mouse ortholog of DYF-2, WDR19, also localizes to cilia, pointing to an important evolutionarily conserved role for this WDR protein in cilia development and function.

McGee MD et al. (2006) Mol Biol Cell "UNC-83 IS a KASH protein required for nuclear migration and is recruited to the outer nuclear membrane by a physical interaction with the SUN protein UNC-84."

Rillo R, Starr DA, McGee MD, Anderson AS

[Mol Biol Cell, 2006]

Monitoring Editor: Erika Holzbaur UNC-84 is required to localize UNC-83 to the nuclear envelope where it functions during nuclear migration. A KASH domain in UNC-83 was identified. KASH domains are conserved in the nuclear envelope proteins Syne/nesprins, Klarsicht, MSP-300, and ANC-1. C. elegans UNC-83 was shown to localize to the outer nuclear membrane and UNC-84 to the inner nuclear membrane in transfected mammalian cells, suggesting the KASH and SUN protein targeting mechanisms are conserved. Deletion of the KASH domain of UNC-83 blocked nuclear migration and localization to the C. elegans nuclear envelope. Some point mutations in the UNC-83 KASH domain disrupted nuclear migration, even if they localized normally. At least two separable portions of the C-terminal half of UNC-84 were found to interact with the UNC-83 KASH domain in a membrane-bound, split-ubiquitin yeast two-hybrid system. However, the SUN domain was essential for UNC-84 function and UNC-83 loclization in vivo. These data support the model that KASH and SUN proteins bridge the nuclear envelope, connecting the nuclear lamina to cytoskeletal components. This mechanism appears conserved across eukaryotes and is the first proposed mechanism to target proteins specifically to the outer nuclear membrane.

Qadota H et al. (2007) Mol Biol Cell "Two LIM domain proteins and UNC-96 link UNC-97/pinch to myosin thick filaments in Caenorhabditis elegans muscle."

Kaibuchi K, Benian GM, Mercer KB, Miller RK, Qadota H

[Mol Biol Cell, 2007]

Monitoring Editor: Erika Holzbaur By yeast two hybrid screening, we found three novel interactors (UNC-95, LIM-8, and LIM-9) for UNC-97/PINCH in C. elegans. All three proteins contain LIM domains that are required for binding. Among the three interactors, LIM-8 and LIM-9 also bind to UNC-96, a component of sarcomeric M-lines. UNC-96 and LIM-8 also bind to the C-terminal portion of a myosin heavy chain, MHC A, which resides in the middle of thick filaments in the proximity of M-lines. All interactions identified by yeast two hybrid assays were confirmed by in vitro binding assays using purified proteins. All three novel UNC-97 interactors are expressed in body wall muscle and by antibodies localize to M-lines. Either a decreased or an increased dosage of UNC-96 results in disorganization of thick filaments. Our previous studies showed that UNC-98, a C2H2 Zn finger protein, acts as a linkage between UNC-97, an integrin associated protein, and MHC A in myosin thick filaments. In this study, we demonstrate another mechanism by which this linkage occurs: from UNC-97 through LIM-8 or LIM-9/UNC-96 to myosin.

Qadota H et al. (2008) Mol Biol Cell "A novel protein phosphatase is a binding partner for the protein kinase domains of UNC-89 (Obscurin) in Caenorhabditis elegans."

Ferrara TM, Mercer KB, Qadota H, McGaha LA, Stark TJ, Benian GM

[Mol Biol Cell, 2008]

Monitoring Editor: Erika Holzbaur Mutation of the C. elegans gene unc-89 results in disorganization of muscle A-bands. unc-89 encodes a giant polypeptide (900 kDa) containing two protein kinase domains, PK1 and PK2. Yeast two-hybrid screening using a portion of UNC-89 including PK2, yielded SCPL-1, which contains a CTD phosphatase type domain. In addition to the PK2 domain, interaction with SCPL-1 required the putative autoinhibitory sequence, and Ig and Fn3 domains lying N-terminal of the kinase domain. SCPL-1 also interacts with PK1, and similarly requires the kinase domain and upstream Fn3 and Ig domains. Analogous regions from the two other giant kinases of C. elegans, twitchin and TTN-1, failed to interact with SCPL-1. The interaction between SCPL-1 and either Ig-Fn3-PK2 or Fn3-Ig-PK1 was confirmed by biochemical methods. The scpl-1b promoter is expressed in the same set of muscles as unc-89. Antibodies to SCPL-1 localize to the M-line and a portion of the I-band. Bacterially expressed SCPL-1 proteins have phosphatase activity in vitro with properties similar to previously characterized members of the CTD phosphatase family. RNAi knockdown results in a defect in the function of egg laying muscles. These studies suggest a new role for the CTD phosphatase family, that is, in muscle giant kinase signaling.