Phosphatidylinositol-4-phosphate 5-kinase type 1α attenuates Aβ production by promoting non-amyloidogenic processing of amyloid precursor protein.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Po-Fan WuYung-Feng Liao

Abstract

Alzheimer's disease (AD) is characterized by a chronic decline in cognitive function and is pathologically typified by cerebral deposition of amyloid-β peptide (Aβ). The production of Aβ is mediated by sequential proteolysis of amyloid precursor protein (APP) by β- and γ-secretases, and has been implicated as the essential determinant of AD pathology. Previous studies have demonstrated that the level of phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] in the membrane may potentially modulate Aβ production. Given that PI(4,5)P2 is produced by type 1 phosphatidylinositol-4-phosphate 5-kinases (PIP5Ks), we sought to determine whether the level of PIP5K type Iα (PIP5K1A) can affect production of Aβ by modulating the lipid composition of the membrane. Using a HEK-derived cell line that constitutively expresses yellow fluorescent protein-tagged APP (APP-YFP), we demonstrated that overexpression of PIP5K1A results in significant enhancement of non-amyloidogenic APP processing and a concomitant suppression of the amyloidogenic pathway, leading to a marked decrease in secreted Aβ. Consistently, cells overexpressing PIP5K1A exhibited a significant redistribution of APP-YFP from endosomal compartments to the cell surface. Our findings su...Continue Reading

References

Jun 8, 2001·Annual Review of Biochemistry·B VanhaesebroeckM D Waterfield
Nov 10, 2001·Trends in Biochemical Sciences·D P Brazil, B A Hemmings
Dec 26, 2001·Chemical Reviews·N R LeslieD R Alessi
Apr 19, 2003·The Journal of Biological Chemistry·Renee L DoughmanRichard A Anderson
Aug 20, 2003·The Journal of Cell Biology·Yoshikatsu Aikawa, Thomas F J Martin
Sep 13, 2003·The Journal of Biological Chemistry·Ju-Hyun LeeChristopher C J Miller
Feb 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·Angela Ho, Thomas C Südhof
May 26, 2004·Chemistry & Biology·Glenn D Prestwich
Jul 19, 2005·Physiology·Farah S L ThongAmira Klip
Sep 22, 2005·Proceedings of the National Academy of Sciences of the United States of America·Olav M AndersenThomas E Willnow
Jan 13, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Robert SpoelgenBradley T Hyman
Oct 13, 2006·The Journal of Biological Chemistry·Yoshitake SanoToshiharu Suzuki
Oct 13, 2006·Nature·Gilbert Di Paolo, Pietro De Camilli
Dec 13, 2006·Proceedings of the National Academy of Sciences of the United States of America·Natalie LandmanTae-Wan Kim
Aug 10, 2007·Nature·Giovanni D'AngeloMaria Antonietta De Matteis
Dec 13, 2007·Blood·Federica MicucciRicciarda Galandrini
May 16, 2008·The Journal of Biological Chemistry·Satoko OsawaYasuo Ihara
Jun 10, 2008·The Journal of Biological Chemistry·Pamela OsenkowskiDennis J Selkoe
Sep 12, 2008·The EMBO Journal·Mariella VicinanzaMaria Antonietta De Matteis
Nov 26, 2008·The Journal of Biological Chemistry·Haipeng ChengGopal Thinakaran
Dec 17, 2008·The Journal of Biological Chemistry·Kulandaivelu S VetrivelGopal Thinakaran
Feb 7, 2009·BMJ : British Medical Journal·Alistair Burns, Steve Iliffe
Apr 1, 2009·Experimental Cell Research·Ewelina SzymańskaKatarzyna Kwiatkowska
Jun 11, 2009·The Biochemical Journal·Gerald R V HammondRobin F Irvine
Nov 6, 2009·Journal of Cell Science·Iman van den Bout, Nullin Divecha
Jan 29, 2010·The New England Journal of Medicine·Henry W Querfurth, Frank M LaFerla
Oct 15, 2010·Journal of Cellular Physiology·Yuji FunakoshiYasunori Kanaho
Dec 15, 2010·International Journal of Alzheimer's Disease·Wayne ChadwickStuart Maudsley

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