CPEB1 regulates beta-catenin mRNA translation and cell migration in astrocytes.
A crucial step in directed cell migration is the recruitment of cytoskeletal regulatory and signaling proteins to the leading edge of the cell. One protein localized to the leading edge of a migrating astrocyte is beta-catenin. Using an in vitro wound-healing assay, we show that the localization of beta-catenin to the leading edge is dependent upon new protein synthesis at the time of wounding. We examined the mRNA encoding beta-catenin for potential regulatory elements and identified a conserved cytoplasmic polyadenylation element in the 3'-untranslated region (UTR). We now show that the CPE-binding protein (CPEB1) is expressed in astrocytes and that translation of beta-catenin mRNA is regulated by CPEB1. Further, expression of a mutant CPEB1 protein in astrocytes not only blocks beta-catenin protein localization, it also inhibits cell migration. These findings demonstrate a role for CPEB1-mediated protein synthesis in the localization of beta-catenin protein to the leading edge of migrating astrocytes and in regulating directed cell motility.
Jones
Kendrick J
KJ
Department of Molecular Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520-8103, USA.
Korb
Erica
E
Kundel
Mitchell A
MA
Kochanek
Ashley R
AR
Kabraji
Sheheryar
S
McEvoy
Michael
M
Shin
Chan Y
CY
Wells
David G
DG
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D002464:Cell Migration Inhibition / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D014176:Protein Biosynthesis / Q000502:physiology*; D051381:Rats; D014157:Transcription Factors / Q000502:physiology*; D051176:beta Catenin / Q000096:biosynthesis* / Q000235:genetics*; D039221:mRNA Cleavage and Polyadenylation Factors / Q000502:physiology*
C490386:CPEB1 protein, human; D014157:Transcription Factors; D051176:beta Catenin; D039221:mRNA Cleavage and Polyadenylation Factors