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.
Zhao, Yanmei; Tan, Chieh-Hsiang; Krauchunas, Amber; Scharf, Andrea; Dietrich, Nicholas; Warnhoff, Kurt; Yuan, Zhiheng; Druzhinina, Marina; Gu, Sam Guoping; Miao, Long; Singson, Andrew; Ellis, Ronald E; and Kornfeld, Kerry, "The Zinc Transporter ZIPT-7.1 Regulates Sperm Activation in Nematodes" (2018). School of Osteopathic Medicine Faculty Scholarship. 130.
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Zhao Y, Tan CH, Krauchunas A, Scharf A, Dietrich N, Warnhoff K, Yuan Z, Druzhinina M, Gu SG, Miao L, Singson A, Ellis RE, Kornfeld K. The zinc transporter ZIPT-7.1 regulates sperm activation in nematodes. PloS Biology. 2018 Jun 7;16(6):e2005069. eCollection 2018 Jun. doi: 10.1371/journal.pbio.2005069. PMID: 29879108. PMCID: PMC5991658.
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