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

Abstract

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.

ACKNOWLEDGMENTS

We thank R. Homayouni (University of Tennessee Health Center, Memphis) for several APP and APLP clones and J. Manley for CPSF antibody. Y.-S.H. was supported by a fellowship from the Charles A. King Trust.

This work was supported by grants from the NIH. Core support from the Diabetes Endocrinology Research Center Program Project (DK32520) is also gratefully acknowledged.