Liu, Chenshu et al. (2021) International Worm Meeting "Rewiring quality control in C.elegans meiosis using a new chemically-induced proximity system"

Liu, Chenshu, Dernburg, Abby F.

[International Worm Meeting, 2021]

During the extended meiotic prophase, homologous chromosomes must pair, culminating with the assembly of synaptonemal complex (SC) along their lengths (synapsis). Synapsis is essential for crossover formation between homologs, and thus for their accurate segregation. In C.elegans, defects in synapsis are monitored by a quality control program called the synapsis checkpoint, as one or more pairs of unsynapsed chromosomes lead to a cell cycle delay and can eventually trigger apoptosis. Previous work from our lab revealed that the synapsis checkpoint requires the presence of unsynapsed pairing centers (PCs), special regions on each chromosome that promote homolog pairing and synapsis. However, how cells detect defects in SC assembly remains unknown. In C.elegans, the Polo-like kinase PLK-2 shows dynamic subnuclear localization during meiotic prophase: it is first recruited to PCs during early prophase, and following synapsis it relocalizes to the SC. This suggests that the localization of PLK-2 might be part of the signal that triggers the synapsis checkpoint. To test this idea, we deployed a new chemically-induced proximity (CIP) system that we engineered by modifying a core component of the auxin-inducible degradation system. We engineered mutations into the F-box protein TIR1 to prevent it from interacting with other ubiquitin ligase components. By fusing one protein to this TIR1 sequence and another to a "degron" peptide, we can induce proximity between the two tagged proteins using the small molecule indole acetic acid (auxin). With this system, we successfully targeted PLK-2 to specific chromosomal/nuclear structures. We found that ectopic targeting of PLK-2 to X-chromosomal PCs following synapsis was sufficient to induce apoptosis. Importantly, such induced apoptosis did not require HUS-1, an essential component of the DNA damage checkpoint, but was abrogated by mutation of PCH-2, an essential component of the synapsis checkpoint. By combining this CIP system with various meiotic mutants, I will also discuss about how PLK-2 coordinates with other meiotic kinases and the nucleoskeleton during meiotic quality control and cell cycle progression. Together, we have developed a simple, versatile CIP system and leveraged it to better understand the mechanisms underlying meiotic progression and quality control. This CIP system will enable a wide variety of new experiments in C. elegans and other model organisms.

Liu, Chenshu et al. (2021) International Worm Meeting "Nuclear lamina cooperates with inner nuclear membrane proteins to counteract LINC-mediated forces during oogenesis in C. elegans"

Wang, John, Dernburg, Abby F., Liu, Chenshu, Wu, Fan, Lung, Zoe

[International Worm Meeting, 2021]

The nuclear lamina is essential to protect genome integrity from mechanical stress. This requirement is more stringent in some tissues and developmental events. During oogenesis, meiotic nuclei are situated in a stressful environment filled with cytoskeletons. The nuclear lamina, consisting of the lamin proteins, is a conserved component of the nuclear envelope that can confer mechanical rigidity to the meiotic nuclei. C.elegans expresses a single lamin protein, LMN-1, which is similar to mammalian B-type lamin. Loss of LMN-1 results in near-complete sterility, with hypercondensed chromatin observed in many germline nuclei. The exact functions of LMN-1 in meiotic nuclei during oogenesis, however, remains unclear. Using the auxin-inducible degradation system, we found that acute depletion of LMN-1 in C.elegans germline recapitulated nuclear collapse seen in lmn-1 homozygotes during late stages of meiotic prophase. LMN-1 depletion also led to persistent DNA double strand breaks and elevated apoptosis, but germline apoptosis is neither sufficient nor required for nuclear collapse. We further observed prolonged and excessive clustering of the LINC complex proteins SUN-1 and ZYG-12 at the nuclear envelope (NE) upon LMN-1 acute depletion. Importantly, co-depletion of SUN-1 or ZYG-12, or inhibition of dynein-mediated forces, rescued the nuclear collapse triggered by acute LMN-1 depletion. By contrast, co-depletion of the inner nuclear membrane proteins EMR-1/LEM-2 or SAMP-1 rendered nuclei susceptible to collapse even earlier, at the time of meiotic entry. Live imaging demonstrated that shrinkage of the NE preceded chromosome hypercondensation during nuclear collapse, and that before NE shrinkage happened, LINC complex asymmetrically redistribute to one side of the NE in a dynein-dependent manner. Finally, the connection between the pairing center regions of the chromosomes and the NE, albeit being important for LINC complex function during homolog pairing, is dispensable for nuclear collapse caused by LMN-1 depletion. Together our results suggest that lamin cooperates with additional inner nuclear membrane proteins to protect meiotic nuclei from collapse by antagonizing forces exerted by dynein and transmitted through the LINC complex during oogenesis. Our work has also established an inducible system for modeling laminopathy.

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.

Kirkwood TB (2013) Cell Metab "Untangling functional declines in the locomotion of aging worms."

Kirkwood TB

[Cell Metab, 2013]

All physiological functions decline with age, but which changes are primary and which are secondary is not always clear. Liu et al. (2013), examining functional changes in the muscles and motor neurons of C. elegans, suggest that when it comes to locomotion, it is the nervous system that shows earlier age-related deterioration.

David S Peal et al. (2001) International C. elegans Meeting "Chemical and Genetic Inhibition of Sulfation in C. elegans"

David S Peal, Laura L Kiessling

[International C. elegans Meeting, 2001]

In order to examine the process of sulfation in C. elegans, sulfation was inhibited chemically using sodium chlorate, and genetically using the process of RNA-mediated interference (RNAi). Sodium chlorate inhibition during early larval stages resulted in a dose-dependant developmental delay. BLAST searches of characterized sulfotransferases against the worm genome resulted in the identification of 4 putative sulfotransferases: C34F6.4 and F08B4.6 (previously identified: [1] and [2]), F40H3.5, and Y34B4A.e. RNAi of the putative N-deacetylase/N-sulfotransferase F08B4.6 resulted in "stacking" of eggs in the gonad, along with eggs laid at the 2- and 4-celled stage. RNAi of the putative hexuronic 2-O sulfotransferase C34F6.4 resulted in a shortened, bulbous gonad. These initial results indicate that sulfation may be important during development of C. elegans. [1] Shworak, NW, Liu, J, Fritze, LMS, Schwartz, JJ, Zhang, L, Logeart, D, Rosenberg, RD. JBC 272: 28008-19 (1997). [2] Kobayashi, M, Sugumaran, G, Liu, J, Shworak, NW, Silbert, JE, Rosenberg, RD. JBC 274: 10474-80 (1999).

(2024) Development "The people behind the papers - Alyshia Scholl, Yihong Liu and Geraldine Seydoux."

[Development, 2024]

Germ granules have been hypothesized to deliver mRNAs of germ cell fate determinants to primordial germ cells. Now, a new study in Development finds that many mRNAs enriched in germ granules are not involved in germline development in Caenorhabditis elegans. To find out more about the story behind the paper, we caught up with first author Alyshia Scholl, second author Yihong Liu and corresponding author Geraldine Seydoux, Professor at Johns Hopkins University School of Medicine.

Gary Schindelman et al. (2002) West Coast Worm Meeting "Characterization of the sperm transfer step of male mating behavior of Caenorhabditis elegans ."

Gary Schindelman, Allyson J Whittaker, Shahla Gharib, Paul W Sternberg

[West Coast Worm Meeting, 2002]

C. elegans male mating behavior involves the proper execution of a series of sub-behaviors culminating in the transfer of sperm to the hermaphrodite (Liu, KS and Sternberg, PW. 1995. Neuron 14:79-89). These sub-behaviors are: Response to hermaphrodite, backing, turning, vulval location, spicule insertion and sperm transfer. We are analyzing the genetic control of this stereotyped behavior as it may provide insight into sensory perception and nervous system function.

Skora S et al. (2013) EMBO J "Life(span) in balance: oxygen fuels a sophisticated neural network for lifespan homeostasis in C. elegans."

Zimmer M, Skora S

[EMBO J, 2013]

A key finding of modern ageing research is that our limitation in lifespan is more than the result of accumulated organismal decay. Lifespan is regulated by genetically defined chemosensory and endocrine pathways, which integrate signals that reflect the internal and external status of the animal. New findings by Liu and Cai unravel a role for the environmental gases oxygen and carbon dioxide in the regulation of lifespan homeostasis and thus a novel function of oxygen-chemosensory neurons in C. elegans.