Membrane-associated cytoplasmic granules carrying the Argonaute protein WAGO-3 enable paternal epigenetic inheritance in Caenorhabditis elegans.

Epigenetic inheritance describes the transmission of gene regulatory information across generations without altering DNA sequences, enabling offspring to adapt to environmental conditions. Small RNAs have been implicated in this, through both the oocyte and the sperm. However, as much of the cellular content is extruded during spermatogenesis, it is unclear whether cytoplasmic small RNAs can contribute to epigenetic inheritance through sperm.

Spermatogenesis.

Most organisms consist of two cell lineages - somatic cells and germ cells. The former are required for the current generation, and the latter create offspring. Male and female germ cells are usually produced during spermatogenesis and oogenesis, which take place in the testis and the ovary, respectively.

Gamete interactions require transmembranous immunoglobulin-like proteins with conserved roles during evolution.

class genes are male germline-enriched in their expression and indispensable during sperm-oocyte fusion. Identification of mammalian orthologs that exhibit similar functions to these genes has been a challenge. The mouse gene encodes a sperm-specific, immunoglobulin (Ig)-like transmembrane (TM) protein that is required for gamete fusion.

The Immunoglobulin-like Gene spe-45 Acts during Fertilization in Caenorhabditis elegans like the Mouse Izumo1 Gene.

The Caenorhabditis elegans spe-9 class genes, which show specific or predominant expression in the male germline, are indispensable for fertilization [1, 2]. However, due to the rapid evolution of genes involved in reproduction, we do not currently know if there are spe-9 class genes in mammals that play similar roles during fertilization to those found in C. elegans.

Role of posttranslational modifications in C. elegans and ascaris spermatogenesis and sperm function.

Generally, spermatogenesis and sperm function involve widespread posttranslational modification of regulatory proteins in many different species. Nematode spermatogenesis has been studied in detail, mostly by genetic/molecular genetic techniques in the free-living Caenorhabditis elegans and by biochemistry/cell biology in the pig parasite Ascaris suum. Like other nematodes, both of these species produce sperm that use a form of amoeboid motility termed crawling, and many aspects of spermatogenesis are likely to be similar in both species.

Vps33b pathogenic mutations preferentially affect VIPAS39/SPE-39-positive endosomes.

Mutations in Vps33 isoforms cause pigment dilution in mice (Vps33a, buff) and Drosophila (car) and the neurogenic arthrogryposis, renal dysfunction and cholestasis syndrome in humans (ARC1, VPS33B). The later disease is also caused by mutations in VIPAS39, (Vps33b interacting protein, apical-basolateral polarity regulator, SPE-39 homolog; ARC2), a protein that interacts with the HOmotypic fusion and Protein Sorting (HOPS) complex, a tether necessary for endosome-lysosome traffic. These syndromes offer insight into fundamental endosome traffic processes unique to metazoans.

Developmental genetics of secretory vesicle acidification during Caenorhabditis elegans spermatogenesis.

Secretory vesicles are used during spermatogenesis to deliver proteins to the cell surface. In Caenorhabditis elegans, secretory membranous organelles (MO) fuse with the plasma membrane to transform spermatids into fertilization-competent spermatozoa. We show that, like the acrosomal vesicle of mammalian sperm, MOs undergo acidification during development.

Nematode sperm maturation triggered by protease involves sperm-secreted serine protease inhibitor (Serpin).

Spermiogenesis is a series of poorly understood morphological, physiological and biochemical processes that occur during the transition of immotile spermatids into motile, fertilization-competent spermatozoa. Here, we identified a Serpin (serine protease inhibitor) family protein (As_SRP-1) that is secreted from spermatids during nematode Ascaris suum spermiogenesis (also called sperm activation) and we showed that As_SRP-1 has two major functions. First, As_SRP-1 functions in cis to support major sperm protein (MSP)-based cytoskeletal assembly in the spermatid that releases it, thereby facilitating sperm motility acquisition.

Metazoan cell biology of the HOPS tethering complex.

Membrane fusion with vacuoles, the lysosome equivalent of the yeast Saccharomyces cerevisiae, is among the best understood membrane fusion events. Our precise understanding of this fusion machinery stems from powerful genetics and elegant in vitro reconstitution assays. Central to vacuolar membrane fusion is the multi-subunit tether the HO motypic fusion and Protein Sorting (HOPS) complex, a complex of proteins that organizes other necessary components of the fusion machinery.

Clathrin-dependent mechanisms modulate the subcellular distribution of class C Vps/HOPS tether subunits in polarized and nonpolarized cells.

Coats define the composition of carriers budding from organelles. In addition, coats interact with membrane tethers required for vesicular fusion. The yeast AP-3 (Adaptor Protein Complex 3) coat and the class C Vps/HOPS (HOmotypic fusion and Protein Sorting) tether follow this model as their interaction occurs at the carrier fusion step.

Spermatogenesis-defective (spe) mutants of the nematode Caenorhabditis elegans provide clues to solve the puzzle of male germline functions during reproduction.

In most species, each sex produces gametes, usually either sperm or oocytes, from its germline during gametogenesis. The sperm and oocyte subsequently fuse together during fertilization to create the next generation. This review focuses on spermatogenesis and the roles of sperm during fertilization in the nematode Caenorhabditis elegans, where suitable mutants are readily obtained.

The CIL-1 PI 5-phosphatase localizes TRP Polycystins to cilia and activates sperm in C. elegans.

Background: C. elegans male sexual behaviors include chemotaxis and response to hermaphrodites, backing, turning, vulva location, spicule insertion, and sperm transfer, culminating in cross-fertilization of hermaphrodite oocytes with male sperm. The LOV-1 and PKD-2 transient receptor potential polycystin (TRPP) complex localizes to ciliated endings of C.

The genetics and cell biology of spermatogenesis in the nematode C. elegans.

Creation of mutants that affect spermatogenesis is very challenging in most experimental systems, especially mammals. The main reason this is true is because "absence of successful mating" is a negative result that can occur for a wide variety of trivial, irrelevant reasons. The C.

SPE-39 family proteins interact with the HOPS complex and function in lysosomal delivery.

Yeast and animal homotypic fusion and vacuole protein sorting (HOPS) complexes contain conserved subunits, but HOPS-mediated traffic in animals might require additional proteins. Here, we demonstrate that SPE-39 homologues, which are found only in animals, are present in RAB5-, RAB7-, and RAB11-positive endosomes where they play a conserved role in lysosomal delivery and probably function via their interaction with the core HOPS complex. Although Caenorhabditis elegans spe-39 mutants were initially identified as having abnormal vesicular biogenesis during spermatogenesis, we show that these mutants also have disrupted processing of endocytosed proteins in oocytes and coelomocytes.

Spermatogenesis.

Spermatogenesis creates functional sperm from an initially undifferentiated germ cell. In the nematode Caenorhabditis elegans, both males and hermaphrodites engage in spermatogenesis. The hermaphrodite germ line, like that of the male, initiates spermatogenesis during the L4 larval stage.

spe-10 encodes a DHHC-CRD zinc-finger membrane protein required for endoplasmic reticulum/Golgi membrane morphogenesis during Caenorhabditis elegans spermatogenesis.

C. elegans spermatogenesis employs lysosome-related fibrous body-membranous organelles (FB-MOs) for transport of many cellular components. Previous work showed that spe-10 mutants contain FB-MOs that prematurely disassemble, resulting in defective transport of FB components into developing spermatids.

The spe-42 gene is required for sperm-egg interactions during C. elegans fertilization and encodes a sperm-specific transmembrane protein.

Fertilization, the union of sperm and egg to form a new organism, is a critical process that bridges generations. Although the cytological and physiological aspects of fertilization are relatively well understood, little is known about the molecular interactions that occur between gametes. C.

Dynamic localization of SPE-9 in sperm: a protein required for sperm-oocyte interactions in Caenorhabditis elegans.

Background: Fertilization in Caenorhabditis elegans requires functional SPE-9 protein in sperm. SPE-9 is a transmembrane protein with a predicted extracellular domain that contains ten epidermal growth factor (EGF)-like motifs. The presence of these EGF-like motifs suggests that SPE-9 is likely to function in gamete adhesive and/or ligand-receptor interactions.

The Caenorhabditis elegans spe-39 gene is required for intracellular membrane reorganization during spermatogenesis.

Caenorhabditis elegans spermatid formation involves asymmetric partitioning of cytoplasm during the second meiotic division. This process is mediated by specialized ER/Golgi-derived fibrous body-membranous organelles (FB-MOs), which have a fibrous body (FB) composed of bundled major sperm protein filaments and a vesicular membranous organelle (MO). spe-39 mutant spermatocytes complete meiosis but do not usually form spermatids.

Dominant mutations in the Caenorhabditis elegans Myt1 ortholog wee-1.3 reveal a novel domain that controls M-phase entry during spermatogenesis.

Regulatory phosphorylation of the Cdc2p kinase by Wee1p-type kinases prevents eukaryotic cells from entering mitosis or meiosis at an inappropriate time. The canonical Wee1p kinase is a soluble protein that functions in the eukaryotic nucleus. All metazoa also have a membrane-associated Wee1p-like kinase named Myt1, and we describe the first genetic characterization of this less well-studied kinase.