Abstract:
:Dominant mutations in presenilin1 (PS1) and presenilin2 (PS2) are a major cause of early-onset Alzheimer's disease. In this report we analyze the expression of the zebrafish presenilin1 (Psen1) and presenilin2 (Psen2) proteins during embryogenesis. We demonstrate that Psen1 and Psen2 holoproteins are relatively abundant in zebrafish embryos and are proteolytically processed. Psen1 is maternally expressed, whereas Psen2 is expressed at later stages during development. The Psen1 C-terminal proteolytic fragment (CTF) is present at varying levels during embryogenesis, indicating the existence of developmental control mechanisms regulating its production. We examine the codependency of Psen1 and Psen2 expression during early embryogenesis. Forced overexpression of psen2 increases expression of Psen2 holoprotein, but not the N-terminal fragment (NTF), indicating that levels of Psen2 NTF are strictly controlled. Overexpression of psen2 did not alter levels of Psen1 holoprotein, CTF, or higher molecular weight complexes. Reduction of Psen1 activity in zebrafish embryos produces similar developmental defects to those seen for loss of PS1 activity in knockout mice. The relevance of these results to previous work on presenilin protein regulation and function are discussed. Our work shows that zebrafish embryos are a valid and valuable system in which to study presenilin interactions, regulation, and function.
journal_name
Exp Cell Resjournal_title
Experimental cell researchauthors
Nornes S,Groth C,Camp E,Ey P,Lardelli Mdoi
10.1016/s0014-4827(03)00257-xkeywords:
subject
Has Abstractpub_date
2003-09-10 00:00:00pages
124-32issue
1eissn
0014-4827issn
1090-2422pii
S001448270300257Xjournal_volume
289pub_type
杂志文章abstract::Skin extracellular matrix (ECM) molecules regulate a variety of cellular activities, including cell movement, which are central to wound healing and metastasis. Regulated cell movement is modulated by proteases and their associated molecules, including the serine proteases urinary-type plasminogen activator (uPA) and ...
journal_title:Experimental cell research
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abstract::The retinoblastoma tumor suppressor protein (RB) is activated/dephosphorylated to mediate cell cycle inhibition in response to antimitogenic signals. To elucidate the mode of RB action at this critical transition, we utilized cell lines that can be induced to express a constitutively active allele of RB (PSM-RB). As e...
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journal_title:Experimental cell research
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journal_title:Experimental cell research
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journal_title:Experimental cell research
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journal_title:Experimental cell research
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journal_title:Experimental cell research
pub_type: 杂志文章
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journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1999.4767
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doi:10.1016/j.yexcr.2006.01.009
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journal_title:Experimental cell research
pub_type: 杂志文章
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journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2008.12.023
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pub_type: 杂志文章
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journal_title:Experimental cell research
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journal_title:Experimental cell research
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journal_title:Experimental cell research
pub_type: 杂志文章
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journal_title:Experimental cell research
pub_type: 杂志文章
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journal_title:Experimental cell research
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journal_title:Experimental cell research
pub_type: 杂志文章
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journal_title:Experimental cell research
pub_type: 杂志文章
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