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https://hdl.handle.net/2440/2992
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Type: | Journal article |
Title: | Developmental control of Presenilin1 expression, endoproteolysis, and interaction in zebrafish embryos |
Author: | Nornes, S. Groth, C. Camp-Dotlic, E. Ey, P. Lardelli, M. |
Citation: | Experimental Cell Research, 2003; 289(1):124-132 |
Publisher: | Academic Press Inc |
Issue Date: | 2003 |
ISSN: | 0014-4827 1090-2422 |
Organisation: | Centre for the Molecular Genetics of Development |
Statement of Responsibility: | Svanhild Nornes, Casper Groth, Esther Camp, Peter Ey and Michael Lardelli |
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. |
Keywords: | Alzheimer’s disease Notch Somitogenesis Presenilin Zebrafish Embryo development |
Description: | Copyright © 2003 Elsevier Science (USA). All rights reserved. |
DOI: | 10.1016/S0014-4827(03)00257-X |
Description (link): | http://www.sciencedirect.com/science/journal/00144827 |
Published version: | http://dx.doi.org/10.1016/s0014-4827(03)00257-x |
Appears in Collections: | Aurora harvest 2 Centre for the Molecular Genetics of Development publications Molecular and Biomedical Science publications |
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