C. elegans sperm bud vesicles to deliver a meiotic maturation signal to distant oocytes

Sperm from different species have evolved distinctive motility structures, including tubulin-based flagella in mammals and major sperm protein (MSP)-based pseudopods in nematodes. Despite such divergence, we show that sperm-specific PP1 phosphatases, which are required for male fertility in mouse, function in multiple processes in the development and motility of Caenorhabditis elegans amoeboid sperm. We used live-imaging analysis to show the PP1 phosphatases GSP-3 and GSP-4 (GSP-3/4) are required to partition chromosomes during sperm meiosis. Postmeiosis, tracking fluorescently labeled sperm revealed that both male and hermaphrodite sperm lacking GSP-3/4 are immotile. Genetic and in vitro activation assays show lack of GSP-3/4 causes defects in pseudopod development and the rate of pseudopodial treadmilling. Further, GSP-3/4 are required for the localization dynamics of MSP. GSP-3/ 4 shift localization in concert with MSP from fibrous bodies that sequester MSP at the base of the pseudopod, where directed MSP disassembly facilitates pseudopod contraction. Consistent with a role for GSP-3/4 as a spatial regulator of MSP disassembly, MSP is mislocalized in sperm lacking GSP-3/4. Although a requirement for PP1 phosphatases in nematode and mammalian sperm suggests evolutionary conservation, we show PP1s have independently evolved sperm-specific paralogs in separate lineages. Thus PP1 phosphatases are highly adaptable and employed across a broad range of sexually reproducing species to regulate male fertility.

Section: Analysis Of Gsp-3/4 Protein Levelsmentioning

confidence: 99%

Section: Immunohistochemistrymentioning

confidence: 99%

Sperm Development and Motility are Regulated by PP1 Phosphatases inCaenorhabditis elegans

Samson

et al. 2012

“…The -2 oocyte then moves into the -1 position where it will undergo maturation/ovulation $23 min later. In hermaphrodites with sperm, the signal that triggers maturation/ovulation is constitutive: the major sperm protein (MSP) secreted from sperm (McCarter et al 1999;Miller et al 2001;Kosinski et al 2005). By contrast, in animals without sperm (sex determination mutant females, adult hermaphrodites that have exhausted their self-sperm), oocytes form but are arrested in diakinesis.…”

Section: Introductionmentioning

confidence: 99%

Multiple Functions and Dynamic Activation of MPK-1 Extracellular Signal-Regulated Kinase Signaling inCaenorhabditis elegansGermline Development

Lee

Ohmachi

Arur³

et al. 2007

180

338

The raison d'etre of the germline is to produce oocytes and sperm that pass genetic material and cytoplasmic constituents to the next generation. To achieve this goal, many developmental processes must be executed and coordinated. ERK, the terminal MAP kinase of a number of signaling pathways, controls many aspects of development. Here we present a comprehensive analysis of MPK-1 ERK in Caenorhabditis elegans germline development. MPK-1 functions in four developmental switches: progression through pachytene, oocyte meiotic maturation/ovulation, male germ cell fate specification, and a nonessential function of promoting the proliferative fate. MPK-1 also regulates multiple aspects of cell biology during oogenesis, including membrane organization and morphogenesis: organization of pachytene cells on the surface of the gonadal tube, oocyte organization and differentiation, oocyte growth control, and oocyte nuclear migration. MPK-1 activation is temporally/spatially dynamic and most processes appear to be controlled through sustained activation. MPK-1 thus may act not only in the control of individual processes but also in the coordination of contemporaneous processes and the integration of sequential processes. Knowledge of the dynamic activation and diverse functions of MPK-1 provides the foundation for identification of upstream signaling cascades responsible for region-specific activation and the downstream substrates that mediate the various processes. I N the generation of oocytes and sperm, perhaps the most complex cells in animals, the germline lineage undergoes a multifaceted developmental process that begins in embryogenesis and continues into adulthood. While the details of the steps can differ between species due to differences in reproductive biology, a core set of events occurs in animals: germ cell fate specification, incorporation into the gonad, sexual fate specification, proliferative expansion, and gamete production. Two interconnected differentiation programs define gamete production: (1) meiosis where chromosomes pair, recombine, and then segregate to give a reassorted haploid content and (2) gametogenesis where biosynthetic and morphogenetic processes generate the large nutrient and developmental information-rich oocyte and the small motile sperm. In aggregate, these processes are essential to pass genetic material from generation to generation and to form the totipotent zygote necessary for the development of a new individual. Disruption of germline development can lead to sterility, germline tumors, and birth defects. Thus an important goal is to define the pathways and gene products that control and execute the various steps of germline development.The MAP kinase extracellular signal-regulated kinase (ERK) functions in many aspects of animal development and homeostasis (Marshall 1995;Rubin et al. 1997;Schlessinger 2000;Sundaram 2006). ERK is the terminal regulator of signaling cascades such as canonical receptor tyrosine kinase signaling, which contains core members, including the RA...

“…Bivalents are then connected only by crossovers and sister-chromatid cohesion (Schvarzstein et al 2010). Late diakinesis nuclei cellularize to form oocytes and remain arrested with six bivalents until ovulation is triggered by sperm (Miller et al 2001;Kosinski et al 2005).The germline of kin-18 mutants was smaller with reduced numbers of nuclei per zone compared to wild type ( Figure 1I and Table S1). Without having a marker for meiotic progression that can differentiate all of the meiotic stages it is difficult to assess which nuclei are at any particular meiotic stage in kin-18 mutants.…”

mentioning

confidence: 99%

“…Then a signal from sperm, mediated by the major sperm protein, triggers the activation of MPK-1 in the proximal diakinesis oocyte. This activation leads to exit from meiotic prophase I and to the initiation of ovulation and the meiotic divisions (Miller et al 2001;Kosinski et al 2005). Thousand And One (TAO) kinases were originally identified as mammalian homologs of Ste20 protein kinase in Saccharomyces cerevisiae (Hutchison et al 1998;Chen et al 1999).…”

mentioning

confidence: 99%

Coordination of Recombination with Meiotic Progression in the Caenorhabditis elegans Germline by KIN-18, a TAO Kinase That Regulates the Timing of MPK-1 Signaling

Yin¹,

Donlevy²,

Smolikove

2015

Meiosis is a tightly regulated process requiring coordination of diverse events. A conserved ERK/MAPK-signaling cascade plays an essential role in the regulation of meiotic progression. The Thousand And One kinase (TAO) kinase is a MAPK kinase kinase, the meiotic role of which is unknown. We have analyzed the meiotic functions of KIN-18, the homolog of mammalian TAO kinases, in Caenorhabditis elegans. We found that KIN-18 is essential for normal meiotic progression; mutants exhibit accelerated meiotic recombination as detected both by analysis of recombination intermediates and by crossover outcome. In addition, ectopic germ-cell differentiation and enhanced levels of apoptosis were observed in kin-18 mutants. These defects correlate with ectopic activation of MPK-1 that includes premature, missing, and reoccurring MPK-1 activation. Late progression defects in kin-18 mutants are suppressed by inhibiting an upstream activator of MPK-1 signaling, KSR-2. However, the acceleration of recombination events observed in kin-18 mutants is largely MPK-1-independent. Our data suggest that KIN-18 coordinates meiotic progression by modulating the timing of MPK-1 activation and the progression of recombination events. The regulation of the timing of MPK-1 activation ensures the proper timing of apoptosis and is required for the formation of functional oocytes. Meiosis is a conserved process; thus, revealing that KIN-18 is a novel regulator of meiotic progression in C. elegans would help to elucidate TAO kinase's role in germline development in higher eukaryotes.KEYWORDS KIN-18; MPK-1; TAO; meiosis; recombination; genetics of sex T HE germline contains a multitude of cells that proliferate to form a population that will undergo two meiotic divisions, giving rise to gametes. In meiosis, one round of DNA replication is followed by two cell divisions reducing the ploidy of the germ cell by half. A large fraction of the cells encompassing the germline are found in meiotic prophase I. Many of the key evolutionarily conserved events that take place in this specialized prophase are aimed at preparing chromosomes for their segregation in meiosis I. One such essential and conserved event is the formation of crossovers between homologous chromosomes. During the initial stages of meiotic prophase I (leptotene/zygotene), a protein structure named the synaptonemal complex (SC) starts to assemble between homologs (MacQueen et al. 2002;Schild-Prufert et al. 2011). Concurrently, meiotic DNA double-strand breaks (DSBs) are introduced to initiate meiotic recombination (Keeney et al. 1997;Dernburg et al. 1998). As meiosis progresses, germ cells enter pachytene where the SC is fully formed and meiotic DSBs are processed and repaired. In the presence of a fully formed SC, meiotic DSBs are repaired, giving rise to crossovers by late pachytene. In most multicellular organisms, apoptosis is activated in late pachytene and reduces the number of germ cells in the developing germline (Gumienny et al. 1999). Apoptosis serves as a quality control...