The cytosolic loop of the gamma-secretase component presenilin enhancer 2 protects zebrafish embryos from apoptosis

The Journal of Biological Chemistry
Henrik ZetterbergWeiming Xia

Abstract

The gamma-secretase complex, composed of presenilin, presenilin enhancer 2 (Pen-2), nicastrin, and Aph-1, catalyzes the final cleavage of amyloid precursor protein to generate the toxic amyloid beta protein, the major component of plaques in the brains of Alzheimer disease patients. To understand the in vivo function of Pen-2, we used morphant technology available in zebrafish and transiently knocked down the expression of endogenous Pen-2 by injecting the morpholino (MO) against Pen-2. Two truncated Pen-2 proteins lacking either the cytosolic or the C-terminal domain were expressed in MO-injected embryos. This deletion analysis demonstrated that the Pen-2 cytosolic loop is essential for protecting developing embryos from caspase-dependent apoptosis caused by the reduction of Pen-2. Twelve amino acids in the C terminus of Pen-2 were dispensable and could not rescue the Pen-2 knockdown-induced apoptotic phenotype. Surprisingly, double knockdown of Pen-2 and nuclear factor kappaB component p65 abrogated the single Pen-2 MO-induced caspase activation, indicating that a previously reported pro-apoptotic role of NF-kappaB in some cell types could be manifested in a whole animal and that knockdown of Pen-2 may trigger pro-apoptotic a...Continue Reading

References

Jul 2, 1992·Nature·D P Lane
Jul 5, 1991·Science·M HollsteinC C Harris
Mar 13, 1986·Biochemical and Biophysical Research Communications·T TamaokiF Tomita
Mar 10, 1995·Science·H Steller
Dec 6, 1994·Proceedings of the National Academy of Sciences of the United States of America·A Lorenzo, B A Yankner
Apr 1, 1994·Experimental Cell Research·R BertrandY Pommier
Jul 1, 1995·Developmental Dynamics : an Official Publication of the American Association of Anatomists·C B KimmelT F Schilling
Feb 1, 1996·Current Opinion in Genetics & Development·S Bates, K H Vousden
Apr 30, 1999·Science·S Artavanis-TsakonasR J Lake
Dec 22, 1999·Oncogene·M Barkett, T D Gilmore
Mar 9, 2000·Journal of Virology·J L ConnollyT S Dermody
Apr 14, 2000·Brain Pathology·G S RobertsonJ B Schulz
Nov 23, 2000·Genes & Development·R Kopan, A Goate
Mar 29, 2001·Physiological Reviews·D J Selkoe
Apr 6, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·Y ZhengA A Beg
Sep 7, 2001·Current Opinion in Cell Biology·M E Fortini
Mar 20, 2002·Current Neurology and Neuroscience Reports·W Xia
Jan 11, 2003·The Journal of Biological Chemistry·Wen-jie LuoHuaxi Xu
Mar 28, 2003·Nature·Nobumasa TakasugiTakeshi Iwatsubo
Apr 8, 2003·Nature Cell Biology·Dieter EdbauerChristian Haass
May 13, 2003·Proceedings of the National Academy of Sciences of the United States of America·W Taylor KimberlyDennis J Selkoe
Jun 17, 2003·Journal of Cell Science·Weiming Xia, Michael S Wolfe
Jan 24, 2004·Methods in Cell Science : an Official Journal of the Society for in Vitro Biology·Brian Key, Christine A Devine
Jun 1, 2004·Molecular and Cellular Biology·Ricardo G CorreaInder M Verma
Aug 12, 2004·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Javier F Negron, Richard A Lockshin
Nov 13, 2004·The Journal of Biological Chemistry·Seong-Hun Kim, Sangram S Sisodia

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Citations

Feb 22, 2008·Neuroinformatics·Tianming LiuStephen T C Wong
Apr 16, 2010·Zebrafish·Alexandra AbramssonHenrik Zetterberg
Jun 1, 2007·Biomarkers in Medicine·Ulf AndreassonHenrik Zetterberg
Jul 1, 2007·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Diego AlbaniRoberta Pantieri
Jan 11, 2007·Seminars in Cancer Biology·Ujwal J PyatiMatthias Hammerschmidt
Aug 28, 2007·Neurochemistry International·Neville Marks, Martin J Berg
Jun 1, 2020·Ecotoxicology and Environmental Safety·Bo ChengHuiqiang Lu
Nov 9, 2010·Progress in Neurobiology·Paula van TijnPaul J Lucassen

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