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Molecular and Cellular Biology, December 2005, p. 10930-10939, Vol. 25, No. 24
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.24.10930-10939.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Amyloid Precursor Proteins Anchor CPEB to Membranes and Promote Polyadenylation-Induced Translation

Quiping Cao, Yi-Shuian Huang, Ming-Chung Kan, and Joel D. Richter*

Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605

Received 9 August 2005/ Returned for modification 16 September 2005/ Accepted 27 September 2005

The cytoplasmic polyadenylation element (CPE) binding factor, CPEB, is a sequence-specific RNA binding protein that controls polyadenylation-induced translation in germ cells and at postsynaptic sites of neurons. A yeast two-hybrid screen with a mouse brain cDNA library identified the transmembrane amyloid precursor-like protein 1 (APLP1) as a CPEB-interacting factor. CPEB binds the small intracellular domain (ICD) of APLP1 and the related proteins APLP2 and APP. These proteins promote polyadenylation and translation by stimulating Aurora A catalyzed CPEB serine 174 phosphorylation. Surprisingly, CPEB, Maskin, CPSF, and several other factors involved in polyadenylation and translation and CPE-containing RNA are all detected on membranes by cell fractionation and immunoelectron microscopy. Moreover, most of the RNA that undergoes polyadenylation does so in membrane-containing fractions. These data demonstrate a link between cytoplasmic polyadenylation and membrane association and implicate APP family member proteins as anchors for localized mRNA polyadenylation and translation.


* Corresponding author. Mailing address: Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation St., Suite 204, Worcester, MA 01605. Phone: (508) 856-8615. Fax: (508) 856-4289. E-mail: joel.richter{at}umassmed.edu.


Molecular and Cellular Biology, December 2005, p. 10930-10939, Vol. 25, No. 24
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.24.10930-10939.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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