Development, Vol 124, Issue 11 2167-2177, Copyright © 1997 by Company of Biologists

JOURNAL ARTICLES

The NIMA-related kinase 2, Nek2, is expressed in specific stages of the meiotic cell cycle and associates with meiotic chromosomes

K Rhee and DJ Wolgemuth
Department of Genetics and Development, The Center for Reproductive Sciences, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.

The Aspergillus nimA gene encodes a Ser/Thr protein kinase which is required for mitosis, in addition to Cdc2, and which has been suggested to have a role in chromosomal condensation. In this study, we isolated a potential murine homologue of nimA, Nek2, which was shown to be expressed most abundantly in the testis of the adult tissues examined. Its expression in the testis was restricted to the germ cells, with highest levels detected in spermatocytes at pachytene and diplotene stages. Immunohistochemical analysis revealed that Nek2 localized to nuclei, exhibiting a non-uniform distribution within the nucleus. Nek2 appeared to be associated with meiotic chromosomes, an association that was better defined by immunolocalization to hypotonically dispersed meiotic chromosomes. This localization was more apparent in regions of dense chromatin, including the sex vesicle, and was also obvious at some of the chromosome ends. The presence of Nek2 protein was not unique to male germ cells, as it was found in meiotic pachytene stage oocytes as well. Furthermore, in an in vitro experimental setting in which meiotic chromosome condensation was induced with okadaic acid, a concomitant induction of Nek2 kinase activity was observed. The expression of Nek2 in meiotic prophase is consistent with the hypothesis that in vivo, Nek2 is involved in the G2/M phase transition of the cell cycle. Our results further provide evidence that in vivo, mouse Nek2 is involved in events of meiosis, including but not limited to chromosomal condensation.

This article has been cited by other articles:

				T. Almog, S. Lazar, N. Reiss, N. Etkovitz, E. Milch, N. Rahamim, M. Dobkin-Bekman, R. Rotem, M. Kalina, J. Ramon, et al. Identification of Extracellular Signal-regulated Kinase 1/2 and p38 MAPK as Regulators of Human Sperm Motility and Acrosome Reaction and as Predictors of Poor Spermatozoan Quality J. Biol. Chem., May 23, 2008; 283(21): 14479 - 14489. [Abstract] [Full Text] [PDF]

				W. Wu, J. E. Baxter, S. L. Wattam, D. G. Hayward, M. Fardilha, A. Knebel, E. M. Ford, E. F. da Cruz e Silva, and A. M. Fry Alternative Splicing Controls Nuclear Translocation of the Cell Cycle-regulated Nek2 Kinase J. Biol. Chem., September 7, 2007; 282(36): 26431 - 26440. [Abstract] [Full Text] [PDF]

				Y. Jeong, J. Lee, K. Kim, J. C. Yoo, and K. Rhee Characterization of NIP2/centrobin, a novel substrate of Nek2, and its potential role in microtubule stabilization J. Cell Sci., June 15, 2007; 120(12): 2106 - 2116. [Abstract] [Full Text] [PDF]

				L. C. Pradel, M. Bonhivers, N. Landrein, and D. R. Robinson NIMA-related kinase TbNRKC is involved in basal body separation in Trypanosoma brucei J. Cell Sci., May 1, 2006; 119(9): 1852 - 1863. [Abstract] [Full Text] [PDF]

				S. Sonn, I. Khang, K. Kim, and K. Rhee Suppression of Nek2A in mouse early embryos confirms its requirement for chromosome segregation J. Cell Sci., November 1, 2004; 117(23): 5557 - 5566. [Abstract] [Full Text] [PDF]

				S. Di Agostino, F. Botti, A. Di Carlo, C. Sette, and R. Geremia Meiotic progression of isolated mouse spermatocytes under simulated microgravity Reproduction, July 1, 2004; 128(1): 25 - 32. [Abstract] [Full Text] [PDF]

				J. Lee, J. Hong, E. Kim, K. Kim, S. W. Kim, H. Krishnamurthy, S. S.W. Chung, D. J. Wolgemuth, and K. Rhee Developmental stage-specific expression of Rbm suggests its involvement in early phases of spermatogenesis Mol. Hum. Reprod., April 1, 2004; 10(4): 259 - 264. [Abstract] [Full Text] [PDF]

				S. Di Agostino, M. Fedele, P. Chieffi, A. Fusco, P. Rossi, R. Geremia, and C. Sette Phosphorylation of High-Mobility Group Protein A2 by Nek2 Kinase during the First Meiotic Division in Mouse Spermatocytes Mol. Biol. Cell, March 1, 2004; 15(3): 1224 - 1232. [Abstract] [Full Text] [PDF]

				A. H. Osmani, J. Davies, C. E. Oakley, B. R. Oakley, and S. A. Osmani TINA Interacts with the NIMA Kinase in Aspergillus nidulans and Negatively Regulates Astral Microtubules during Metaphase Arrest Mol. Biol. Cell, August 1, 2003; 14(8): 3169 - 3179. [Abstract] [Full Text] [PDF]

				K. I. Swenson, K. E. Winkler, and A. R. Means A New Identity for MLK3 as an NIMA-related, Cell Cycle-regulated Kinase That Is Localized near Centrosomes and Influences Microtubule Organization Mol. Biol. Cell, January 1, 2003; 14(1): 156 - 172. [Abstract] [Full Text]

				M. R. Mahjoub, B. Montpetit, L. Zhao, R. J. Finst, B. Goh, A. C. Kim, and L. M. Quarmby The FA2 gene of Chlamydomonas encodes a NIMA family kinase with roles in cell cycle progression and microtubule severing during deflagellation J. Cell Sci., April 15, 2002; 115(8): 1759 - 1768. [Abstract] [Full Text] [PDF]

				E. Shang, K. Lai, A. I. Packer, J. Paik, W. S. Blaner, M. de Morais Vieira, P. Gouras, and D. J. Wolgemuth Targeted disruption of the mouse cis-retinol dehydrogenase gene: visual and nonvisual functions J. Lipid Res., April 1, 2002; 43(4): 590 - 597. [Abstract] [Full Text] [PDF]

				R. Graf DdNek2, the first non-vertebrate homologue of human Nek2, is involved in the formation of microtubule-organizing centers J. Cell Sci., January 5, 2002; 115(9): 1919 - 1929. [Abstract] [Full Text] [PDF]

				S. Di Agostino, P. Rossi, R. Geremia, and C. Sette The MAPK pathway triggers activation of Nek2 during chromosome condensation in mouse spermatocytes Development, January 4, 2002; 129(7): 1715 - 1727. [Abstract] [Full Text] [PDF]

				D. Escalier Genetic approach to male meiotic division deficiency: the human macronuclear spermatozoa Mol. Hum. Reprod., January 1, 2002; 8(1): 1 - 7. [Abstract] [Full Text] [PDF]

				D. J. Wolgemuth, E. Laurion, and K. M. Lele Regulation of the Mitotic and Meiotic Cell Cycles in the Male Germ Line Recent Prog. Horm. Res., January 1, 2002; 57(1): 75 - 101. [Abstract] [Full Text] [PDF]

				A. Fry, P Descombes, C Twomey, R Bacchieri, and E. Nigg The NIMA-related kinase X-Nek2B is required for efficient assembly of the zygotic centrosome in Xenopus laevis J. Cell Sci., January 6, 2000; 113(11): 1973 - 1984. [Abstract] [PDF]

				M. V. Gamble, E. Shang, R. P. Zott, J. R. Mertz, D. J. Wolgemuth, and W. S. Blaner Biochemical properties, tissue expression, and gene structure of a short chain dehydrogenase/ reductase able to catalyze cis-retinol oxidation J. Lipid Res., December 1, 1999; 40(12): 2279 - 2292. [Abstract] [Full Text] [PDF]

				C. Sette, M. Barchi, A. Bianchini, M. Conti, P. Rossi, and R. Geremia Activation of the Mitogen-activated Protein Kinase ERK1 during Meiotic Progression of Mouse Pachytene Spermatocytes J. Biol. Chem., November 19, 1999; 274(47): 33571 - 33579. [Abstract] [Full Text] [PDF]

				A. M. Fry, L. Arnaud, and E. A. Nigg Activity of the Human Centrosomal Kinase, Nek2, Depends on an Unusual Leucine Zipper Dimerization Motif J. Biol. Chem., June 4, 1999; 274(23): 16304 - 16310. [Abstract] [Full Text] [PDF]

				K. Tanaka and E. A. Nigg Cloning and Characterization of the Murine Nek3 Protein Kinase, a Novel Member of the NIMA Family of Putative Cell Cycle Regulators J. Biol. Chem., May 7, 1999; 274(19): 13491 - 13497. [Abstract] [Full Text] [PDF]

				L. Ever, R. Steiner, S. Shalom, and J. Don Two Alternatively Spliced Meig1 Messenger RNA Species Are Differentially Expressed in the Somatic and in the Germ-Cell Compartments of the Testis Cell Growth Differ., January 1, 1999; 10(1): 19 - 26. [Abstract] [Full Text]

				A. M. Fry, T. Mayor, P. Meraldi, Y.-D. Stierhof, K. Tanaka, and E. A. Nigg C-Nap1, a Novel Centrosomal Coiled-Coil Protein and Candidate Substrate of the Cell Cycle-regulated Protein Kinase Nek2 J. Cell Biol., June 29, 1998; 141(7): 1563 - 1574. [Abstract] [Full Text] [PDF]

				K Rhee, M Brunori, V Besset, R Trousdale, and D. Wolgemuth Expression and potential role of Fsrg1, a murine bromodomain-containing homologue of the Drosophila gene female sterile homeotic J. Cell Sci., January 12, 1998; 111(23): 3541 - 3550. [Abstract] [PDF]

				L. Scrittori, F. Hans, D. Angelov, M. Charra, C. Prigent, and S. Dimitrov pEg2 Aurora-A Kinase, Histone H3 Phosphorylation, and Chromosome Assembly in Xenopus Egg Extract J. Biol. Chem., August 3, 2001; 276(32): 30002 - 30010. [Abstract] [Full Text] [PDF]