Abstract
Huntingtin is a ubiquitous cytoplasmic protein. Mutant huntingtin causes Huntington’s disease and its intranuclear inclusion is associated with cytotoxicity. Nuclear localization of normal huntingtin is detected in the oocyte up to 2.5 days post coitum. Therefore, huntingtin is expected to reside in the nucleus even before fertilization. The present study determined normal huntingtin distribution during spermatogenesis. Testicles from an adult male Sprague–Dawley rat were stained with anti-huntingtin antibody and nuclear counterstaining was performed with 4′,6-diamidino-2-phenylindole. Concerning nuclear localization, huntingtin was detected in the spermatids, whereas predominant cytoplasmic localization of it was evident in the spermatogonia. Between the primary and secondary spermatocytes, huntingtin appeared to be delocalized in the nuclei when meiosis occurred. The findings provide evidence that normal huntingtin is transported to the nuclear compartment during the meiotic stage of spermatogenesis.
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References
Group THsDCR (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on huntington’s disease chromosomes. The huntington’s disease collaborative research group. Cell 72(6):971–983
Aziz NA, van Belzen MJ, Coops ID, Belfroid RD, Roos RA (2011) Parent-of-origin differences of mutant htt cag repeat instability in huntington’s disease. Eur J Med Genet 54(4):e413–e418
Yoon SR, Dubeau L, de Young M, Wexler NS, Arnheim N (2003) Huntington disease expansion mutations in humans can occur before meiosis is completed. Proc Natl Acad Sci USA 100(15):8834–8838
Caviston JP, Holzbaur EL (2009) Huntingtin as an essential integrator of intracellular vesicular trafficking. Trends Cell Biol 19(4):147–155
DiFiglia M, Sapp E, Chase KO, Davies SW, Bates GP, Vonsattel JP, Aronin N (1997) Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277(5334):1990–1993
Jeong SJ, Kim M, Chang KA, Kim HS, Park CH, Suh YH (2006) Huntingtin is localized in the nucleus during preimplanatation embryo development in mice. Int J Dev Neurosci 24(1):81–85
Steffan JS, Kazantsev A, Spasic-Boskovic O, Greenwald M, Zhu YZ, Gohler H, Wanker EE, Bates GP, Housman DE, Thompson LM (2000) The huntington’s disease protein interacts with p53 and creb-binding protein and represses transcription. Proc Natl Acad Sci USA 97(12):6763–6768
Nucifora FC Jr, Sasaki M, Peters MF, Huang H, Cooper JK, Yamada M, Takahashi H, Tsuji S, Troncoso J, Dawson VL, Dawson TM, Ross CA et al (2001) Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity. Science 291(5512):2423–2428
Kegel KB, Meloni AR, Yi Y, Kim YJ, Doyle E, Cuiffo BG, Sapp E, Wang Y, Qin ZH, Chen JD, Nevins JR, Aronin N, DiFiglia M (2002) Huntingtin is present in the nucleus, interacts with the transcriptional corepressor c-terminal binding protein, and represses transcription. J Biol Chem 277(9):7466–7476
Zuccato C, Ciammola A, Rigamonti D, Leavitt BR, Goffredo D, Conti L, MacDonald ME, Friedlander RM, Silani V, Hayden MR, Timmusk T, Sipione S, Cattaneo E et al (2001) Loss of huntingtin-mediated bdnf gene transcription in huntington’s disease. Science 293(5529):493–498
Bardin CW (1991) Pituitary-testicular axis. In: Yen SSC, Jaffee RB (eds) Reproductive endocrinology, 3rd edn. WB Saunders, Philadelphia
Acknowledgments
This work was supported by grants from the Korea Health 21 R&D Project (A092058), WCU Neurocytomics and National Research Foundation of Korea (NRF) (2011-0012728).
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Im, W., Chung, J., Lee, ST. et al. Nuclear localization of huntingtin during spermatogenesis. Neurol Sci 35, 459–462 (2014). https://doi.org/10.1007/s10072-013-1515-5
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DOI: https://doi.org/10.1007/s10072-013-1515-5