Overexpression of Human CRB1 or Related Isoforms, CRB2 and CRB3, Does Not Regulate the Human Presenilin Complex in Culture Cells

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• 作者：Rapha&euml ; lle Pardossi-Piquard ; Fusheng Chen ; Nancy F. Silva-Gagliardi ; Michael Szego ; Roderick McInnes ; C. Jane McGlade ; Peter St George-Hyslop ; Paul E. Fraser
• 刊名：Biochemistry
• 出版年：2007
• 出版时间：December 4, 2007
• 年：2007
• 卷：46
• 期：48
• 页码：13704 - 13710
• 全文大小：3232K
• 年卷期：v.46,no.48(December 4, 2007)
• ISSN：1520-4995

文摘

The presenilin proteins (PS1 and PS2) with their partners (NCT, Aph1, and Pen2) are themajor components of the high molecular weight -secretase complex which facilitates the intramembraneouscleavage of various type 1 transmembrane proteins, including the amyloid- precursor protein (APP) andthe Notch receptor. Additional -secretase complex components may be involved in regulation of itsactivity and specificity. A recent investigation indicated that the Crumbs protein is a negative regulatorof Notch signaling and may act by repressing /-secretase activity in Drosophila [Herranz, H., Stamataki,E., Feiguin, F., and Milan, M. (2006) EMBO Rep. 7, 297-302]. To address this question, we investigatedpotential functional interactions between the human Crumbs homologues (CRB1, CRB2, and CRB3) andpresenilin complexes which mediate /-secretase cleavage of APP and Notch. We found no evidence fordirect interaction between CRB1, CRB2, or CRB3 and presenilin complex components. Furthermore,overexpression of human CRB1 and related isoforms, CRB2 and CRB3, had no effect on the levels ofpresenilin complex components, on NCT maturation or on PS endoproteolysis, and did not alter A AICDor NICD production. These results suggest that, in mammalian cells at least, Crumbs is unlikely to be asignificant direct modulator of presenilin-dependent /-secretase activity.