Membrane localization of adenomatous polyposis coli protein at cellular protrusions: targeting sequences and regulation by beta-catenin.

The Journal of Biological Chemistry
Manisha SharmaBeric R Henderson

Abstract

Adenomatous polyposis coli protein (APC) translocates to, and stabilizes, the plus-ends of microtubules. In microtubule-dependent cellular protrusions, APC frequently accumulates in peripheral clusters at the basal membrane. APC targeting to membrane clusters is important for cell migration, but the localization mechanism is poorly understood. In this study, we performed deletion mapping and defined a minimal sequence (amino acids 1-2226) that efficiently targets APC to membrane clusters. This sequence lacks DLG-1 and EB1 binding sites, suggesting that these partners are not absolutely required for APC membrane targeting. A series of APC sequences were transiently expressed in cells and compared for their ability to compete endogenous APC at the membrane; potent inhibition of endogenous APC targeting was elicited by the Armadillo- (binds KAP3A, B56alpha, and ASEF) and beta-catenin-binding domains. The Armadillo domain was predicted to inhibit APC membrane localization through sequestration of the kinesin-KAP3A complex. The role of beta-catenin in APC membrane localization was unexpected but affirmed by overexpressing the APC binding sequence of beta-catenin, which similarly reduced APC membrane staining. Furthermore, we used RN...Continue Reading

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Citations

Jan 27, 2009·Cancer Metastasis Reviews·Mahmut Yilmaz, Gerhard Christofori
Dec 5, 2006·Oncogene·T Akiyama, Y Kawasaki
Apr 13, 2012·Molecular Biology of the Cell·Maria EkmanMaréne Landström
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Dec 20, 2011·Cell Communication & Adhesion·Andrea Buda, Massimo Pignatelli
Dec 15, 2015·Molecular Biology of the Cell·Kate M MillsBeric R Henderson
Sep 3, 2011·Experimental Cell Research·Antony W BurgessRobert G Ramsay
Jun 15, 2011·The International Journal of Biochemistry & Cell Biology·Mariana G BrocardoBeric R Henderson
Oct 5, 2010·The International Journal of Biochemistry & Cell Biology·Michael JohnsonBeric R Henderson
Nov 12, 2015·The International Journal of Biochemistry & Cell Biology·Christina LuiBeric R Henderson
Apr 5, 2008·Seminars in Cell & Developmental Biology·Angela I M BarthW James Nelson
Oct 20, 2011·The Journal of Pathology·Annabelle LewisIan Tomlinson
Aug 21, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Tamar ShultzYoram Altschuler
Oct 11, 2007·Journal of Cell Science·Annette GrohmannJürgen Behrens

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