ERK phosphorylates chromosomal axis component HORMA domain protein HTP-1 to regulate oocyte numbers

Das, Debabrata; Chen, Shin-Yu; Arur, Swathi

doi:10.1126/sciadv.abc5580

Cited by 16 publications

(29 citation statements)

References 56 publications

(97 reference statements)

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“…Moreover, it has been reported that treatment with RA activates ERK1/2 signaling in mouse OGONs (12 dpf) and that this is required to upregulate RA-induced Stra8, a key initiator of meiosis (Kim et al, 2019). The role of ERK activation in C. elegans germ cells has also been linked to meiotic progression, inducing phosphorylation of HTP1 (in human HORMAD1) and SYP-2 (in human SYCEs), which controls the assembly and maintenance of the synaptonemal complex (Nadarajan et al, 2016;Das et al, 2020). Should these mechanisms be conserved in humans, we can speculate that the increased expression of ERKs observed in GONs serves to prepare the cells for meiotic entry.…”

Section: Discussionmentioning

confidence: 99%

Ligand–Receptor Interactions Elucidate Sex-Specific Pathways in the Trajectory From Primordial Germ Cells to Gonia During Human Development

Overeem

CHANG

Spruit

et al. 2021

Front. Cell Dev. Biol.

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The human germ cell lineage originates from primordial germ cells (PGCs), which are specified at approximately the third week of development. Our understanding of the signaling pathways that control this event has significantly increased in recent years and that has enabled the generation of PGC-like cells (PGCLCs) from pluripotent stem cells in vitro. However, the signaling pathways that drive the transition of PGCs into gonia (prospermatogonia in males or premeiotic oogonia in females) remain unclear, and we are presently unable to mimic this step in vitro in the absence of gonadal tissue. Therefore, we have analyzed single-cell transcriptomics data of human fetal gonads to map the molecular interactions during the sex-specific transition from PGCs to gonia. The CellPhoneDB algorithm was used to identify significant ligand–receptor interactions between germ cells and their sex-specific neighboring gonadal somatic cells, focusing on four major signaling pathways WNT, NOTCH, TGFβ/BMP, and receptor tyrosine kinases (RTK). Subsequently, the expression and intracellular localization of key effectors for these pathways were validated in human fetal gonads by immunostaining. This approach provided a systematic analysis of the signaling environment in developing human gonads and revealed sex-specific signaling pathways during human premeiotic germ cell development. This work serves as a foundation to understand the transition from PGCs to premeiotic oogonia or prospermatogonia and identifies sex-specific signaling pathways that are of interest in the step-by-step reconstitution of human gametogenesis in vitro.

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Section: Discussionmentioning

confidence: 99%

Ligand–Receptor Interactions Elucidate Sex-Specific Pathways in the Trajectory From Primordial Germ Cells to Gonia During Human Development

Overeem

CHANG

Spruit

et al. 2021

Front. Cell Dev. Biol.

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“…In C. elegans , the ERK kinase MPK-1 is highly active in early-mid pachytene when it phosphorylates the SC proteins HTP-1 and SYP-2 ( Lee et al, 2007 ; Nadarajan et al, 2016 ; Das et al, 2020 ). HTP-1 phosphorylation on S325 is essential for complete synapsis, as large stretches of chromosomes remain asynapsed in S325A mutants ( Das et al, 2020 ). On the other hand, phosphorylation of SYP-2 prevents breakdown of SC on long chromosome arms ( Nadarajan et al, 2016 ).…”

Section: Chromosome Dynamicsmentioning

confidence: 99%

Phospho-Regulation of Meiotic Prophase

Kar

Hochwagen

2021

Front. Cell Dev. Biol.

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Germ cells undergoing meiosis rely on an intricate network of surveillance mechanisms that govern the production of euploid gametes for successful sexual reproduction. These surveillance mechanisms are particularly crucial during meiotic prophase, when cells execute a highly orchestrated program of chromosome morphogenesis and recombination, which must be integrated with the meiotic cell division machinery to ensure the safe execution of meiosis. Dynamic protein phosphorylation, controlled by kinases and phosphatases, has emerged as one of the main signaling routes for providing readout and regulation of chromosomal and cellular behavior throughout meiotic prophase. In this review, we discuss common principles and provide detailed examples of how these phosphorylation events are employed to ensure faithful passage of chromosomes from one generation to the next.

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“…Category 4 consists of three genes, htp-1, metr-1 and repo-1 , whose RNAi inactivation increases the survival rate of both WT and the LBP-8::3XFLAG Tg worms. Both HTP-1 and REPO-1 are nuclear proteins (18,19). Thus, nuclear proteins are enriched in the candidates that affect lifespan.…”

Section: Resultsmentioning

confidence: 99%

Lipid chaperone LBP-8 coordinates with nuclear factors to promote longevity in Caenorhabditis elegans

Duffy

Zhang

Jung

et al. 2021

Preprint

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Eukaryotic cells are composed of a variety of organelles. Their coordination plays crucial roles in cellular homeostasis and organism longevity and is mediated by proteins with the ability to transport between different organelles. In Caenorhabditis elegans, LBP-8 is a pro-longevity lipid chaperone that can localize to both lysosomes and the nucleus. Here we profiled LBP-8's binding partners using immunoprecipitation and mass spectrometry. From the 45 identified candidates, we discovered four nuclear factors that are required for the LBP-8-induced longevity. Among them, RPC-2, an RNA Polymerase III core subunit, is also necessary for the nuclear localization of LBP-8. Moreover, we have screened nuclear transport machinery components, and revealed the requirement of the nuclear import, not export, for the LBP-8 longevity effects. Together, these results suggest that the lipid chaperone LBP-8 relies on specific nuclear factors to retain in the nucleus and regulate longevity.

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ERK phosphorylates chromosomal axis component HORMA domain protein HTP-1 to regulate oocyte numbers

Cited by 16 publications

References 56 publications

Ligand–Receptor Interactions Elucidate Sex-Specific Pathways in the Trajectory From Primordial Germ Cells to Gonia During Human Development

Ligand–Receptor Interactions Elucidate Sex-Specific Pathways in the Trajectory From Primordial Germ Cells to Gonia During Human Development

Phospho-Regulation of Meiotic Prophase

Lipid chaperone LBP-8 coordinates with nuclear factors to promote longevity in Caenorhabditis elegans

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