Sperm Development and Motility are Regulated by PP1 Phosphatases in<i>Caenorhabditis elegans</i>

Wu, Jan‐Jan; Go, Aiza C.; Samson, Mark; Cintra, Thais; Mirsoian, Susan; Wu, Tammy F.; Jow, Margaret M.; Routman, Eric J.; Chu, Diana S.

doi:10.1534/genetics.111.135376

Cited by 53 publications

(62 citation statements)

References 73 publications

(76 reference statements)

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“…These two genes are highly similar (98% identity) and dsRNA directed against either gene is expected to target both. GSP-3/4 is required for spermatid activation, possibly by altering the polymerization dynamics of cytoskeletal MSP within the sperm cytoplasm (Wu et al 2012). We raised antibodies to a C-terminal region of GSP-3/4 and confirmed the previously reported localization pattern in the sperm ( Figure 8B and Figure S5).…”

Section: Postmeiotic Degradation Of Memi Proteins Requires a Cullin-rsupporting

confidence: 85%

“…The yeast PP1 phosphatase GLC7 is involved in glycogen metabolism, meiosis, sporulation, and mitosis (Feng et al 1991;Peggie et al 2002;Tan et al 2003;Bharucha et al 2008). GSP-3/4 are required for multiple C. elegans sperm functions, including the development and motility of sperm, as well as chromosome segregation in sperm meiosis (Chu et al 2006;Wu et al 2012). PP1 phosphatases are also necessary for sperm development and fertility in mice (Varmuza et al 1999;Oppedisano et al 2002;Chakrabarti et al 2007).…”

Section: Discussionmentioning

confidence: 99%

“…PP1 phosphatases are also necessary for sperm development and fertility in mice (Varmuza et al 1999;Oppedisano et al 2002;Chakrabarti et al 2007). Interestingly, GSP-3/4 co-localizes with MSP (major sperm protein) (Wu et al 2012), the cytoskeletal protein required for both the ameboid crawling of C. elegans sperm as well as the diffusible signal for oocyte maturation (Burke and Ward 1983;Sepsenwol et al 1989;Miller et al 2001;Kosinski et al 2005).…”

Section: Discussionmentioning

confidence: 99%

“…From 16,000 genes tested, two suppressors were identified, gsp-3 and gsp-4 ( Figure 8A). Both genes encode a sperm-specific PP1 phosphatase related to GLC seven protein phosphatases (Wu et al 2012). These two genes are highly similar (98% identity) and dsRNA directed against either gene is expected to target both.…”

Section: Postmeiotic Degradation Of Memi Proteins Requires a Cullin-rmentioning

confidence: 99%

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Maternal MEMI Promotes Female Meiosis II in Response to Fertilization in Caenorhabditis elegans

Ataeian

Tegha-Dunghu

Curtis³

et al. 2016

Genetics

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In most animals, female meiosis completes only after fertilization. Sperm entry has been implicated in providing a signal for the initiation of the final meiotic processes; however, a maternal component required for this process has not been previously identified. We report the characterization of a novel family of three highly similar paralogs (memi-1, memi-2, memi-3) that encode oocyte-specific proteins. A hyper-morphic mutation memi-1(sb41) results in failure to exit female meiosis II properly; however, loss of all three paralogs results in a "skipped meiosis II" phenotype. Mutations that prevent fertilization, such as fer-1(hc1), also cause a skipped meiosis II phenotype, suggesting that the MEMI proteins represent a maternal component of a postfertilization signal that specifies the meiosis II program. MEMI proteins are degraded before mitosis and sensitive to ZYG-11, a substrate-specific adapter for cullin-based ubiquitin ligase activity, and the memi-1(sb41) mutation results in inappropriate persistence of the MEMI-1 protein into mitosis. Using an RNAi screen for suppressors of memi-1(sb41), we identified a sperm-specific PP1 phosphatase, GSP-3/4, as a putative sperm component of the MEMI pathway. We also found that MEMI and GSP-3/4 proteins can physically interact via co-immunoprecipitation. These results suggest that sperm-specific PP1 and maternal MEMI proteins act in the same pathway after fertilization to facilitate proper meiosis II and the transition into embryonic mitosis.

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Section: Postmeiotic Degradation Of Memi Proteins Requires a Cullin-rsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Postmeiotic Degradation Of Memi Proteins Requires a Cullin-rmentioning

confidence: 99%

See 2 more Smart Citations

Maternal MEMI Promotes Female Meiosis II in Response to Fertilization in Caenorhabditis elegans

Ataeian

Tegha-Dunghu

Curtis³

et al. 2016

Genetics

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“…To find sperm factors that tie into the MEMI pathway, the authors used RNAi screening to identify two suppressors of the original memi-1(sb41) mutant: gsp-3 and gsp-4 (henceforth referred to as gsp-3/4), two nearly identical PP1 phosphatase homologs (Chu et al 2006). GSP-3/4 are highly expressed during spermatogenesis, and required for sperm meiosis and motility (Wu et al 2012). To rule out the possibility that oocytes contribute GSP-3/4, the authors treated memi-1(sb41) mutant hermaphrodites with gsp-3/4 RNAi, and crossed them to wild-type males.…”

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confidence: 99%

Parental Control Begins at the Beginning

Chu

2016

Genetics

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In this commentary, Diana Chu considers the findings of Ataeian et al. (2016) in this issue of GENETICS in the context of parental contributions to development. This work reveals how molecular players contributed by oocyte and sperm coordinate early transitions in the embryo.N ew parents anticipate their job begins at birth. Little do they know they have been exerting control within the baby's first cell since fertilization. At that moment, sperm entry unleashes a torrent of molecular changes crucial for development. A key transition is forming the diploid DNA complement from paternal and maternal DNA. Sperm bring their haploid share to the oocyte; however, preparing the maternal haploid portion is carefully staged. Oocytes, which can be stored for years in some organisms, arrest prior to meiotic divisions until receiving a signal to begin meiotic maturation (Figure 1). Oocytes start meiotic divisions but arrest again until fertilization signals egg activation. At that point, meiotic divisions complete, and the cell transitions to mitosis. This transition from oocyte to embryo is vital-the cell must sense that the paternal DNA is in the house before completing the meiotic divisions. The molecules that coordinate these early events are largely mysterious in any organism, due in part to the difficulty of observing fertilization within living organisms. In this issue, Ataeian et al. (2016) exploit tools offered by the transparent model organism Caenorhabditis elegans to identify and characterize maternal and paternal molecular components that together convey that fertilization has occurred, and embryonic development is ready to proceed.The maternal part of the story began with a classical temperaturesensitive genetic screen in C. elegans performed 20 years ago to identify genes important for embryonic development (Mitenko et al. 1997). Ataeian et al. (2016) focus on a dominant maternal effect lethal mutant called sb41. Examining an sb41 strain expressing fluorescently tagged histone and tubulin proteins revealed that oocytes do not transition to embryos properlythey fail to complete the second meiotic division, do not form a second polar body, and enter mitosis with the wrong complement of maternal DNA. Subsequently, the cell fails to complete mitosis and dies. Based on this phenotype, the authors dub the affected gene memi-1 (meiosis-to-mitosis transition defect).Whole genome sequencing of the mutant allowed researchers to molecularly characterize memi-1. Database searches revealed two C. elegans paralogs, named memi-2 and memi-3, that share 87% identity with memi-1 but have no conserved domains. Genetic and RNAi analyses showed that single mutants or knockdowns of individual memi genes exhibit no phenotypes, whereas reducing expression of at least two memi paralogs together causes embryonic lethality, supporting the view that MEMI proteins work redundantly. This function is regulated in a cell cycledependent manner, as MEMI levels are high in oocytes but low in mitosis. The authors show that ubiquitin-mediated pr...

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The molecular underpinnings of fertility: Genetic approaches in Caenorhabditis elegans

Mei

Singson

2020

Advanced Genetics

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The study of mutations that impact fertility has a catch-22. Fertility mutants are often lost since they cannot simply be propagated and maintained. This has hindered progress in understanding the genetics of fertility. In mice, several molecules are found to be required for the interactions between the sperm and egg, with JUNO and IZUMO1 being the only known receptor pair on the egg and sperm surface, respectively. In Caenorhabditis elegans, a total of 12 proteins on the sperm or oocyte have been identified to mediate gamete interactions. Majority of these genes were identified through mutants isolated from genetic screens. In this review, we summarize the several key screening strategies that led to the identification of fertility mutants in C. elegans and provide a perspective about future research using genetic approaches. Recently, advancements in new technologies such as high-throughput sequencing and Crispr-based genome editing tools have accelerated the molecular, cell biological, and mechanistic analysis of fertility genes. We review how these valuable tools advance our understanding of the molecular underpinnings of fertilization. We draw parallels of the molecular mechanisms of fertilization between worms and mammals and argue that our work in C. elegans complements fertility research in humans and other species.

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Sperm Development and Motility are Regulated by PP1 Phosphatases inCaenorhabditis elegans

Cited by 53 publications

References 73 publications

Maternal MEMI Promotes Female Meiosis II in Response to Fertilization in Caenorhabditis elegans

Maternal MEMI Promotes Female Meiosis II in Response to Fertilization in Caenorhabditis elegans

Parental Control Begins at the Beginning

The molecular underpinnings of fertility: Genetic approaches in Caenorhabditis elegans

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