Subcellular localization of presenilins during mouse preimplantation development.
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
SJ
*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 Kore.
Kim
H S
HS
Chang
K A
KA
Geum
D H
DH
Park
C H
CH
Seo
J H
JH
Rah
J C
JC
Lee
J H
JH
Choi
S H
SH
Lee
S G
SG
Kim
K
K
Suh
Y H
YH
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry; D016373:DNA, Antisense / Q000494:pharmacology; D004622:Embryo, Mammalian / Q000737:chemistry / Q000187:drug effects; D047108:Embryonic Development; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000032:analysis* / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D008870:Microtubules / Q000737:chemistry; D009154:Mutation; D011247:Pregnancy; D053764:Presenilin-1; D053766:Presenilin-2; D016196:S Phase
D016373:DNA, Antisense; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; C067713:lactacystin; D000111:Acetylcysteine