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. 2002 May;161(1):143–155. doi: 10.1093/genetics/161.1.143

Spermiogenesis initiation in Caenorhabditis elegans involves a casein kinase 1 encoded by the spe-6 gene.

Paul J Muhlrad 1, Samuel Ward 1
PMCID: PMC1462088  PMID: 12019230

Abstract

Immature spermatids from Caenorhabditis elegans are stimulated by an external activation signal to reorganize their membranes and cytoskeleton to form crawling spermatozoa. This rapid maturation, termed spermiogenesis, occurs without any new gene expression. To better understand this signal transduction pathway, we isolated suppressors of a mutation in the spe-27 gene, which is part of the pathway. The suppressors bypass the requirement for spe-27, as well as three other genes that act in this pathway, spe-8, spe-12, and spe-29. Eighteen of the suppressor mutations are new alleles of spe-6, a previously identified gene required for an early stage of spermatogenesis. The original spe-6 mutations are loss-of-function alleles that prevent major sperm protein (MSP) assembly in the fibrous bodies of spermatocytes and arrest development in meiosis. We have isolated the spe-6 gene and find that it encodes a predicted protein-serine/threonine kinase in the casein kinase 1 family. The suppressor mutations appear to be reduction-of-function alleles. We propose a model whereby SPE-6, in addition to its early role in spermatocyte development, inhibits spermiogenesis until the activation signal is received. The activation signal is transduced through SPE-8, SPE-12, SPE-27, and SPE-29 to relieve SPE-6 repression, thus triggering the formation of crawling spermatozoa.

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Selected References

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  1. Achanzar W. E., Ward S. A nematode gene required for sperm vesicle fusion. J Cell Sci. 1997 May;110(Pt 9):1073–1081. doi: 10.1242/jcs.110.9.1073. [DOI] [PubMed] [Google Scholar]
  2. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  3. Altschul S. F., Madden T. L., Schäffer A. A., Zhang J., Zhang Z., Miller W., Lipman D. J. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997 Sep 1;25(17):3389–3402. doi: 10.1093/nar/25.17.3389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Anderson P. Mutagenesis. Methods Cell Biol. 1995;48:31–58. [PubMed] [Google Scholar]
  5. Burke D. J., Ward S. Identification of a large multigene family encoding the major sperm protein of Caenorhabditis elegans. J Mol Biol. 1983 Nov 25;171(1):1–29. doi: 10.1016/s0022-2836(83)80312-x. [DOI] [PubMed] [Google Scholar]
  6. Cegielska A., Gietzen K. F., Rivers A., Virshup D. M. Autoinhibition of casein kinase I epsilon (CKI epsilon) is relieved by protein phosphatases and limited proteolysis. J Biol Chem. 1998 Jan 16;273(3):1357–1364. doi: 10.1074/jbc.273.3.1357. [DOI] [PubMed] [Google Scholar]
  7. Chung S., Gumienny T. L., Hengartner M. O., Driscoll M. A common set of engulfment genes mediates removal of both apoptotic and necrotic cell corpses in C. elegans. Nat Cell Biol. 2000 Dec;2(12):931–937. doi: 10.1038/35046585. [DOI] [PubMed] [Google Scholar]
  8. Driscoll M. Cell death in C. elegans: molecular insights into mechanisms conserved between nematodes and mammals. Brain Pathol. 1996 Oct;6(4):411–425. doi: 10.1111/j.1750-3639.1996.tb00873.x. [DOI] [PubMed] [Google Scholar]
  9. Edgley M. L., Baillie D. L., Riddle D. L., Rose A. M. Genetic balancers. Methods Cell Biol. 1995;48:147–184. [PubMed] [Google Scholar]
  10. Gietzen K. F., Virshup D. M. Identification of inhibitory autophosphorylation sites in casein kinase I epsilon. J Biol Chem. 1999 Nov 5;274(45):32063–32070. doi: 10.1074/jbc.274.45.32063. [DOI] [PubMed] [Google Scholar]
  11. Graves P. R., Haas D. W., Hagedorn C. H., DePaoli-Roach A. A., Roach P. J. Molecular cloning, expression, and characterization of a 49-kilodalton casein kinase I isoform from rat testis. J Biol Chem. 1993 Mar 25;268(9):6394–6401. [PubMed] [Google Scholar]
  12. Gross S. D., Anderson R. A. Casein kinase I: spatial organization and positioning of a multifunctional protein kinase family. Cell Signal. 1998 Nov;10(10):699–711. doi: 10.1016/s0898-6568(98)00042-4. [DOI] [PubMed] [Google Scholar]
  13. Hall D. H., Gu G., García-Añoveros J., Gong L., Chalfie M., Driscoll M. Neuropathology of degenerative cell death in Caenorhabditis elegans. J Neurosci. 1997 Feb 1;17(3):1033–1045. doi: 10.1523/JNEUROSCI.17-03-01033.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hanks S. K., Quinn A. M., Hunter T. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science. 1988 Jul 1;241(4861):42–52. doi: 10.1126/science.3291115. [DOI] [PubMed] [Google Scholar]
  15. Hodgkin J. Genetic nomenclature guide. Caenorhabditis elegans. Trends Genet. 1995 Mar;:24–25. [PubMed] [Google Scholar]
  16. Hoekstra M. F., Liskay R. M., Ou A. C., DeMaggio A. J., Burbee D. G., Heffron F. HRR25, a putative protein kinase from budding yeast: association with repair of damaged DNA. Science. 1991 Aug 30;253(5023):1031–1034. doi: 10.1126/science.1887218. [DOI] [PubMed] [Google Scholar]
  17. Horvitz H. R., Brenner S., Hodgkin J., Herman R. K. A uniform genetic nomenclature for the nematode Caenorhabditis elegans. Mol Gen Genet. 1979 Sep;175(2):129–133. doi: 10.1007/BF00425528. [DOI] [PubMed] [Google Scholar]
  18. Italiano J. E., Jr, Stewart M., Roberts T. M. How the assembly dynamics of the nematode major sperm protein generate amoeboid cell motility. Int Rev Cytol. 2001;202:1–34. doi: 10.1016/s0074-7696(01)02002-2. [DOI] [PubMed] [Google Scholar]
  19. Italiano J. E., Jr, Stewart M., Roberts T. M. Localized depolymerization of the major sperm protein cytoskeleton correlates with the forward movement of the cell body in the amoeboid movement of nematode sperm. J Cell Biol. 1999 Sep 6;146(5):1087–1096. doi: 10.1083/jcb.146.5.1087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jeanmougin F., Thompson J. D., Gouy M., Higgins D. G., Gibson T. J. Multiple sequence alignment with Clustal X. Trends Biochem Sci. 1998 Oct;23(10):403–405. doi: 10.1016/s0968-0004(98)01285-7. [DOI] [PubMed] [Google Scholar]
  21. Karlsson R., Zheng J., Xuong N., Taylor S. S., Sowadski J. M. Structure of the mammalian catalytic subunit of cAMP-dependent protein kinase and an inhibitor peptide displays an open conformation. Acta Crystallogr D Biol Crystallogr. 1993 Jul 1;49(Pt 4):381–388. doi: 10.1107/S0907444993002306. [DOI] [PubMed] [Google Scholar]
  22. Kloss B., Price J. L., Saez L., Blau J., Rothenfluh A., Wesley C. S., Young M. W. The Drosophila clock gene double-time encodes a protein closely related to human casein kinase Iepsilon. Cell. 1998 Jul 10;94(1):97–107. doi: 10.1016/s0092-8674(00)81225-8. [DOI] [PubMed] [Google Scholar]
  23. Kramer J. M., French R. P., Park E. C., Johnson J. J. The Caenorhabditis elegans rol-6 gene, which interacts with the sqt-1 collagen gene to determine organismal morphology, encodes a collagen. Mol Cell Biol. 1990 May;10(5):2081–2089. doi: 10.1128/mcb.10.5.2081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lewis J. A., Fleming J. T. Basic culture methods. Methods Cell Biol. 1995;48:3–29. [PubMed] [Google Scholar]
  25. Machaca K., DeFelice L. J., L'Hernault S. W. A novel chloride channel localizes to Caenorhabditis elegans spermatids and chloride channel blockers induce spermatid differentiation. Dev Biol. 1996 May 25;176(1):1–16. doi: 10.1006/dbio.1996.9999. [DOI] [PubMed] [Google Scholar]
  26. Murakami A., Kimura K., Nakano A. The inactive form of a yeast casein kinase I suppresses the secretory defect of the sec12 mutant. Implication of negative regulation by the Hrr25 kinase in the vesicle budding from the endoplasmic reticulum. J Biol Chem. 1999 Feb 5;274(6):3804–3810. doi: 10.1074/jbc.274.6.3804. [DOI] [PubMed] [Google Scholar]
  27. Nance J., Davis E. B., Ward S. spe-29 encodes a small predicted membrane protein required for the initiation of sperm activation in Caenorhabditis elegans. Genetics. 2000 Dec;156(4):1623–1633. doi: 10.1093/genetics/156.4.1623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Nance J., Minniti A. N., Sadler C., Ward S. spe-12 encodes a sperm cell surface protein that promotes spermiogenesis in Caenorhabditis elegans. Genetics. 1999 May;152(1):209–220. doi: 10.1093/genetics/152.1.209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Nelson G. A., Ward S. Vesicle fusion, pseudopod extension and amoeboid motility are induced in nematode spermatids by the ionophore monensin. Cell. 1980 Feb;19(2):457–464. doi: 10.1016/0092-8674(80)90520-6. [DOI] [PubMed] [Google Scholar]
  30. Plowman G. D., Sudarsanam S., Bingham J., Whyte D., Hunter T. The protein kinases of Caenorhabditis elegans: a model for signal transduction in multicellular organisms. Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13603–13610. doi: 10.1073/pnas.96.24.13603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Reinke V., Smith H. E., Nance J., Wang J., Van Doren C., Begley R., Jones S. J., Davis E. B., Scherer S., Ward S. A global profile of germline gene expression in C. elegans. Mol Cell. 2000 Sep;6(3):605–616. doi: 10.1016/s1097-2765(00)00059-9. [DOI] [PubMed] [Google Scholar]
  32. Rivers A., Gietzen K. F., Vielhaber E., Virshup D. M. Regulation of casein kinase I epsilon and casein kinase I delta by an in vivo futile phosphorylation cycle. J Biol Chem. 1998 Jun 26;273(26):15980–15984. doi: 10.1074/jbc.273.26.15980. [DOI] [PubMed] [Google Scholar]
  33. Roberts T. M., King K. L. Centripetal flow and directed reassembly of the major sperm protein (MSP) cytoskeleton in the amoeboid sperm of the nematode, Ascaris suum. Cell Motil Cytoskeleton. 1991;20(3):228–241. doi: 10.1002/cm.970200306. [DOI] [PubMed] [Google Scholar]
  34. Roberts T. M., Stewart M. Acting like actin. The dynamics of the nematode major sperm protein (msp) cytoskeleton indicate a push-pull mechanism for amoeboid cell motility. J Cell Biol. 2000 Apr 3;149(1):7–12. doi: 10.1083/jcb.149.1.7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Roberts T. M., Stewart M. Nematode sperm locomotion. Curr Opin Cell Biol. 1995 Feb;7(1):13–17. doi: 10.1016/0955-0674(95)80039-5. [DOI] [PubMed] [Google Scholar]
  36. Rowles J., Slaughter C., Moomaw C., Hsu J., Cobb M. H. Purification of casein kinase I and isolation of cDNAs encoding multiple casein kinase I-like enzymes. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9548–9552. doi: 10.1073/pnas.88.21.9548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Shakes D. C., Ward S. Initiation of spermiogenesis in C. elegans: a pharmacological and genetic analysis. Dev Biol. 1989 Jul;134(1):189–200. doi: 10.1016/0012-1606(89)90088-2. [DOI] [PubMed] [Google Scholar]
  38. Varkey J. P., Jansma P. L., Minniti A. N., Ward S. The Caenorhabditis elegans spe-6 gene is required for major sperm protein assembly and shows second site non-complementation with an unlinked deficiency. Genetics. 1993 Jan;133(1):79–86. doi: 10.1093/genetics/133.1.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Ward S., Hogan E., Nelson G. A. The initiation of spermiogenesis in the nematode Caenorhabditis elegans. Dev Biol. 1983 Jul;98(1):70–79. doi: 10.1016/0012-1606(83)90336-6. [DOI] [PubMed] [Google Scholar]
  40. Zhang F., Strand A., Robbins D., Cobb M. H., Goldsmith E. J. Atomic structure of the MAP kinase ERK2 at 2.3 A resolution. Nature. 1994 Feb 24;367(6465):704–711. doi: 10.1038/367704a0. [DOI] [PubMed] [Google Scholar]

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