Amyloid precursor proteins anchor CPEB to membranes and promote polyadenylation-induced translation.
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.
Cao
Quiping
Q
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, 01605, USA
Huang
Yi-Shuian
YS
Kan
Ming-Chung
MC
Richter
Joel D
JD
D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D064096:Aurora Kinase A; D064127:Aurora Kinases; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D015723:Gene Library; D051379:Mice; D009474:Neurons / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D026723:Polyadenylation; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D014157:Transcription Factors; D039221:mRNA Cleavage and Polyadenylation Factors
D016564:Amyloid beta-Protein Precursor; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012694:Serine; C078201:Aplp1 protein, mouse; C576918:Aurka protein, mouse; C490387:Cpeb1 protein, mouse; D014157:Transcription Factors; D039221:mRNA Cleavage and Polyadenylation Factors