A fundamental question in animal development is how motile cells find their correct target destinations. During mating in the nematode Caenorhabditis elegans, males inject sperm through the hermaphrodite vulva into the uterus. Amoeboid sperm crawl around fertilized eggs to the spermatheca--a convoluted tube where fertilization occurs. Here, we show that polyunsaturated fatty acids (PUFAs), the precursors of eicosanoid signalling molecules, function in oocytes to control directional sperm motility within the uterus. PUFAs are transported from the intestine, the site of fat metabolism, to the oocytes yolk, which is a lipoprotein complex. Loss of the RME-2 low-density lipoprotein (LDL) receptor, which mediates yolk endocytosis and fatty acid transport into oocytes, causes severe defects in sperm targeting. We used an RNAi screen to identify lipid regulators required for directional sperm motility. Our results support the hypothesis that PUFAs function in oocytes as precursors of signals that control sperm recruitment to the spermatheca. A common property of PUFAs in mammals and C. elegans is that these fats control local recruitment of motile cells to their target tissues.

SUMMARY Abnormalities in insulin/IGF-1 signaling are associated with infertility, but the molecular mechanisms are not well understood. Here we use liquid chromatography with electrospray ionization tandem mass spectrometry to show that the C. elegans insulin/FOXO pathway regulates the metabolism of locally acting lipid hormones called prostaglandins. C. elegans prostaglandins are synthesized without prostaglandin G/H synthase homologs, the targets of non-steroidal anti-inflammatory drugs. Our results support the model that insulin signaling promotes the conversion of oocyte polyunsaturated fatty acids (PUFAs) into F-series prostaglandins that guide sperm to the fertilization site. Reduction in insulin signaling activates DAF-16/FOXO, which represses the transcription of germline and intestinal genes required to deliver PUFAs to oocytes in lipoprotein complexes. Nutritional and neuroendocrine cues target this mechanism to control prostaglandin metabolism and reproductive output. Prostaglandins may be conserved sperm guidance factors and widespread downstream effectors of insulin actions that influence both reproductive and nonreproductive processes.

The Fc receptor for IgA and IgM (Fcα/μR) is of particular interest because it can bind antibodies of both IgM and IgA isotypes and thus may play a pivotal role in systemic and mucosal immunity. Using IgM and IgA ligands and newly generated Fcα/μR specific monoclonal antibodies we have defined biochemical features and cellular distribution of the human Fcα/μR. Both recombinant and native forms of human Fcα/μR are expressed on the cell surface as remarkably stable homodimeric transmembrane glycoproteins that can bind specifically polymeric IgM or IgA. The only human B cells to express Fcα/μR, albeit at very low levels, are found in the pre‐germinal center subpopulation defined by the IgD+/CD38+ phenotype. Hence the expression pattern differs from that of the mouse wherein Fcα/μR is expressed by both circulating and resident B cell populations. Significantly, the predominant cell type expressing the Fcα/μR in humans is the follicular dendritic cell of germinal centers. The Fcα/μR may thus function in antigen presentation and B cell selection in the germinal center response.

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The genes encoding the murine paired immunoglobulin‐like receptors PIR‐A and PIR‐B are members of a novel gene family which encode cell‐surface receptors bearing immunoreceptor tyrosine‐based inhibitory motifs (ITIMs) and their non‐inhibitory/activatory counterparts. PIR‐A and PIR‐B have highly homologous extracellular domains but distinct trans‐membrane and cytoplasmic regions. A charged arginine in the transmembrane region of PIR‐A suggests its potential association with other transmembrane proteins to form a signal transducing unit. PIR‐B, in contrast, has an uncharged transmembrane region and several ITIMs in its cytoplasmic tail. These characteristics suggest that PIR‐A and PIR‐B which are coordinately expressed by B cells and myeloid cells, serve counter‐regulatory roles in humoral and inflammatory responses. In the present study we have determined the genomic structure of the single copy PIR‐B gene. The gene consists of 15 exons and spans approximately 8 kilobases. The first exon contains the 5′ untranslated region, the ATG translation start site, and approximately half of the leader peptide sequence. The remainder of the leader peptide sequence is encoded by exon 2. Exons 3–8 encode the six extracellular immunoglobulin‐like domains and exons 9 and 10 code for the extracellular membrane proximal and transmembrane regions. The final five exons (exons 11–15) encode for the ITIM‐bearing cytoplasmic tail and the 3′ untranslated region. The intron/exon boundaries of PIR‐B obey the GT‐AG rule and are in phase I, with the notable exception of the three boundaries determined for ITIM‐containing exons. A microsatellite composed of the trinucleotide repeat AAG in the intron between exons 9 and 10 provides a useful marker for studying population genetics.