Zinc: A small molecule with a big impact on sperm function
| Autor: | Marina Druzhinina, Long Miao, Sam Guoping Gu, Nicholas Dietrich, Kurt Warnhoff, Andrew Singson, Zhiheng Yuan, Yanmei Zhao, Ronald E. Ellis, Amber R. Krauchunas, Kerry Kornfeld, Andrea Scharf, Chieh-Hsiang Tan |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Nematoda Cellular differentiation Mutant Cell Membranes Biochemistry Animals Genetically Modified RNA interference Animal Cells Spermatocytes Biology (General) Caenorhabditis elegans Genes Helminth Phylogeny reproductive and urinary physiology biology General Neuroscience Eukaryota Animal Models Spermatids Spermatozoa Cell biology Caenorhabditis Nucleic acids Chemistry Zinc Experimental Organism Systems Genetic interference Caenorhabditis Elegans Physical Sciences Epigenetics Female Signal transduction Cellular Types Cellular Structures and Organelles General Agricultural and Biological Sciences Research Article Chemical Elements Signal Transduction endocrine system QH301-705.5 Research and Analysis Methods Models Biological General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Model Organisms Genetics Animals Amino Acid Sequence Caenorhabditis elegans Proteins Spermatogenesis Ion Transport General Immunology and Microbiology urogenital system Organisms Biology and Life Sciences Membrane Proteins Biological Transport Epistasis Genetic Cell Biology biology.organism_classification Sperm Invertebrates 030104 developmental biology Germ Cells Metabolism Cytoplasm Mutation RNA Gene expression Carrier Proteins Zinc Transporters |
| Zdroj: | PLoS Biology, Vol 16, Iss 6, p e2005069 (2018) PLoS Biology |
| ISSN: | 1545-7885 1544-9173 |
| Popis: | Sperm activation is a fascinating example of cell differentiation, in which immotile spermatids undergo a rapid and dramatic transition to become mature, motile sperm. Because the sperm nucleus is transcriptionally silent, this transition does not involve transcriptional changes. Although Caenorhabditis elegans is a leading model for studies of sperm activation, the mechanisms by which signaling pathways induce this transformation remain poorly characterized. Here we show that a conserved transmembrane zinc transporter, ZIPT-7.1, regulates the induction of sperm activation in Caenorhabditis nematodes. The zipt-7.1 mutant hermaphrodites cannot self-fertilize, and males reproduce poorly, because mutant spermatids are defective in responding to activating signals. The zipt-7.1 gene is expressed in the germ line and functions in germ cells to promote sperm activation. When expressed in mammalian cells, ZIPT-7.1 mediates zinc transport with high specificity and is predominantly located on internal membranes. Finally, genetic epistasis places zipt-7.1 at the end of the spe-8 sperm activation pathway, and ZIPT-7.1 binds SPE-4, a presenilin that regulates sperm activation. Based on these results, we propose a new model for sperm activation. In spermatids, inactive ZIPT-7.1 is localized to the membranous organelles, which contain higher levels of zinc than the cytoplasm. When sperm activation is triggered, ZIPT-7.1 activity increases, releasing zinc from internal stores. The resulting increase in cytoplasmic zinc promotes the phenotypic changes characteristic of activation. Thus, zinc signaling is a key step in the signal transduction process that mediates sperm activation, and we have identified a zinc transporter that is central to this activation process. Author summary Sperm are specialized cells with transcriptionally silent DNA that has been packaged for delivery into the egg. In their final step of development, immature sperm undergo a rapid transition from nonmotile cells to mature, motile sperm capable of fertilization. The signals that trigger this change are not clearly understood. By identifying mutants in the roundworm Caenorhabditis elegans that are defective in sperm activation, we discovered a conserved transmembrane protein, ZIPT-7.1, that transports zinc and promotes sperm activation in both sexes. ZIPT-7.1 is expressed in the germ line and functions there to control sperm activation. When expressed ectopically in mammalian cells, the protein specifically transports zinc across membranes and localizes primarily to membranes within the cell. Previous genetic studies had identified two pathways that mediate sperm activation in C. elegans, and our results suggest that zipt-7.1 acts at the end of one of these two, the spe-8 pathway. We propose that when this pathway triggers sperm activation, it acts through ZIPT-7.1, which mediates the release of zinc from internal stores in the immature sperm. This released zinc functions as a second messenger to promote the differentiation of mature, motile sperm. |
| Databáze: | OpenAIRE |
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