Semenza GL (2001) Cell "HIF-1, O(2), and the 3 PHDs: how animal cells signal hypoxia to the nucleus."

Semenza GL

[Cell, 2001]

Hypoxia-inducible factor 1 (HIF-1) is a global regulator of cellular and systemic O2 homeostasis in animals. A molecular basis for O2 regulated expression of the HIF-1 alpha subunit has now been determined, providing a mechanism for changes in gene expression in response to changes in cellular oxygenation.

Holzbaur E (2010) Curr Biol "Axonal transport: CDKs as traffic signals for motor-ists along the axon?"

Holzbaur E

[Curr Biol, 2010]

A screen for axonal cargo mislocalization in Caenorhabditis elegans neurons implicates the cyclin-dependent kinases CDK-5 and PCT-1 and the cyclin CCY-1 in the regulation of the microtubule motor cytoplasmic dynein.

Shaw R et al. (2009) Cell "PPTR-1 counterAkts insulin signaling."

Shaw R, Dillin A

[Cell, 2009]

The serine/threonine kinase Akt is a focal point in signaling pathways that control cell tumorigenesis and insulin resistance. In this issue, Padmanabhan et al. (2009) identify a phosphatase regulatory subunit PPTR-1 that regulates the insulin/insulin-like growth factor 1 pathway by counteracting Akt activity in worms and mammalian cells.

Yu R et al. (2016) Cell "CSR-1 Slices a Balance."

Yu R, Moazed D

[Cell, 2016]

CSR-1 is a germline-expressed C. elegans Argonaute protein essential for viability. In this issue of Cell, Gerson-Gurwitz et al. now demonstrate a role for CSR-1 and its slicer activity in downregulating the levels of maternally deposited mRNAs to fine-tune the expression of proteins with critical roles in embryonic cell divisions.

Cram EJ (2015) Curr Biol "Mechanotransduction: feeling the squeeze in the C. elegans reproductive system."

Cram EJ

[Curr Biol, 2015]

A new study reports that the RhoGAP SPV-1 senses membrane curvature and cell stretch in the Caenorhabditis elegans spermatheca. Without SPV-1, the cells of the spermatheca are hypercontractile, leading to deformation and rapid ejection of the fertilized eggs. The spermatheca may provide a paradigm for understanding how cells detect mechanical stimuli in vivo.

Shi A et al. (2013) Small GTPases "Interactions between Rab and Arf GTPases regulate endosomal phosphatidylinositol-4,5-bisphosphate during endocytic recycling."

Shi A, Grant BD

[Small GTPases, 2013]

After endocytosis, a selective endocytic recycling process returns many endocytosed molecules back to the plasma membrane. The RAB-10/Rab10 GTPase is known to be a key recycling regulator for specific cargo molecules. New evidence, focused on C. elegans RAB-10 in polarized epithelia, points to a key role of RAB-10 in the regulation of endosomal phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) levels. In turn, PI(4,5)P2 levels strongly influence the recruitment of many peripheral membrane proteins, including those important for vesicle budding through their membrane bending activities. Part of the effect of RAB-10 on endosomal PI(4,5)P2 is through its newly identified effector CNT-1, a predicted GTPase activating protein (GAP) of the small GTPase ARF-6/Arf6. In mammals PI(4,5)P2 generating enzymes are known Arf6 effectors. In C. elegans we found that RAB-10, CNT-1 and ARF-6 are present on the same endosomes, that RAB-10 recruits CNT-1 to endosomes, and that loss of CNT-1 or RAB-10 leads to overaccumulation of endosomal PI(4,5)P2, presumably via hyperactivation of endosomal ARF-6. In turn this leads to over-recruitment of PI(4,5)P2-dependent membrane-bending proteins RME-1/Ehd and SDPN-1/Syndapin/PACSIN. Conversely, in arf-6 mutants, endosomal PI(4,5)P2 levels were reduced and endosomal recruitment of RME-1 and SDPN-1 failed. This work makes an unexpected link between distinct classes of small GTPases that control endocytic recycling, and provides insight into how this interaction affects endosome function at the level of lipid phosphorylation.

Mainpal R et al. (2016) Worm "A twist of fate: How a meiotic protein is providing new perspectives on germ cell development."

Yanowitz JL, Mainpal R

[Worm, 2016]

The molecular pathways that govern how germ line fate is acquired is an area of intense investigation that has major implications for the development of assisted reproductive technologies, infertility interventions, and treatment of germ cell cancers. Transcriptional repression has emerged as a primary mechanism to ensure suppression of somatic growth programs in primordial germ cells. In this commentary, we address how xnd-1 illuminates our understanding of transcriptional repression and how it is coordinated with the germ cell differentiation program. We recently identified xnd-1 as a novel, early determinant of germ cell fates in Caenorhabditis elegans. Our study revealed that XND-1 is maternally deposited into early embryos where it is selectively enriched in the germ lineage and then exclusively found on chromatin in the germ lineage throughout development and into adulthood when it dissociates from chromosomes in late pachytene. This localization is consistent with a range of interesting germ cell defects that suggest xnd-1 is a pivotal determinant of germ cell characteristics. Loss of xnd-1 results in a unique "one PGC (primordial germ cell)" phenotype due to G2 cell cycle arrest of the germline precursor blastomere, P4, which predisposes the animal and its progeny for reduced fecundity. The sterility in xnd-1 mutants is correlated with an increase in the transcriptional activation-associated histone modification, dimethylation of histone H3 lysine 4 (H3K4me2), and aberrant expression of somatic transgenes but overlapping roles with nos-2 and nos-1 suggest that transcriptional repression is achieved by multiple redundant mechanisms.

Gomez TA et al. (2007) Autophagy "Autophagy and insulin/TOR signaling in Caenorhabditis elegans pcm-1 protein repair mutants."

Clarke SG, Gomez TA

[Autophagy, 2007]

Biological responses due to nutrient deprivation in the nematode Caenorhabditis elegans, including L1 diapause and autophagy during dauer formation, can be mediated through the linked DAF-2/insulin/IGF receptor and target-of-rapamycin (TOR) kinase pathways. Here we discuss how altered insulin/TOR signaling may underlie the previously reported phenotypes of worms with a null mutation in the pcm-1 gene that results in reduced autophagy during dauer formation and decreased L1 arrest survival. PCM-1 encodes a protein repair methyltransferase and mutants of the encoding pcm-1 gene are incapable of converting spontaneously damaged l-isoaspartyl residues in cellular proteins to normal forms by this pathway. We speculate that PCM-1 may function either directly or indirectly as an inhibitor of insulin/TOR signaling, perhaps in a role to balance autophagy with alternative protein degradation pathways that may be more specific for recognizing age-damaged proteins.

Rocheleau CE (2012) Curr Biol "RNA interference: Systemic RNAi SIDes with endosomes."

Rocheleau CE

[Curr Biol, 2012]

Systemic RNAi, the intercellular spreading of RNAi silencing, requires SID-1 and SID-3 to import silencing signals in Caenorhabditis elegans. How are these signals exported? SID-5, an endosome-associated protein, is a candidate for the job.

Ellis RE (2020) Curr Biol "Sex Determination: TRA-1 Is a Non-binary Regulator ofSexual Identity."

Ellis RE

[Curr Biol, 2020]

In nematodes, TRA-1 represses the transcription of genes involved in male differentiation, allowing XX animals to undergo normal hermaphrodite development. New reports show that this transcription factor also acts in XO males, to control the differentiation of many neurons.