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Subcellular localization of presenilins during mouse preimplantation development

SUNG-JIN JEONG^*,, HYE-SUN KIM^*, KEUN-A CHANG^*, DONG-HO GEUM, CHEOL HYOUNG PARK^*, JI-HEUI SEO^*, JONG-CHEOL RAH^*, JUN HO LEE^*, SE HOON CHOI^*, SANG GOO LEE, KYUNGJIN KIM and YOO-HUN SUH^*1

^* Department of Pharmacology, College of Medicine and Neuroscience Research Institute, Medical Research Center, Seoul National University, and Biomedical Brain Research Center, Korea National Institute of Health, 110–799 Seoul, South Korea; and
Department of Molecular Biology and Cell Differentiation Research Center, College of Natural Sciences, Seoul National University, 151–742 Seoul, South Korea

¹Correspondence: Department of Pharmacology, College of Medicine, Seoul National University, 28 Yongon-Dong, Chongno-Gu, Seoul 110–799. E-mail: yhsuh{at}plaza.snu.ac.kr

The genes defective in familial Alzheimer’s disease encode the proteins presenilin 1 and 2 (PS1 and 2). Expression of presenilins (PSs) and their proteolytic processing are regulated during neuronal development. Even though these proteins are detected and regulated mainly in Golgi and endoplasmic reticulum, their subcellular distribution during the development is not known. The present study aimed to investigate the localization of PSs and their role during early developmental stage using mouse embryo model. At preimplantation stage, PSs were detected not only in cytoplasm, but also in the nucleus from oocyte to 2.5 dpc (day postcoitum), then disappeared in the nucleus at blastocyst stage (3.5 dpc). Antisense against PS1 and PS2 decreased the transition to blastocyst stage, whereas each antisense alone had no effect. Treatment with lactacystin (26S proteosome inhibitor), which arrest cell cycle at M phase, redistributed PSs into centrosome-kinetochore microtubule. PS2 overexpression in HEK 293 cell arrested cell cycle at S phase. These data suggest that PSs play key roles in cell division and differentiation during early development.—Jeong, S.-J., Kim, H.-S., Chang, K.-A., Geum, D.-H., Park, C. H., Seo, J.-H., Rah, J.-C., Lee, J. H., Choi, S. H., Lee, S. G., Kim, K., Suh, Y.-H. Subcellular localization of presenilins during mouse preimplantation development.

Key Words: preimplantation embryos • nucleus • centrosome-kinetochore microtubule • cell division

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