PLEKHA7 defines an apical junctional complex with cytoskeletal associations and miRNA-mediated growth implications

Cell Cycle
Antonis Kourtidis, Panos Z Anastasiadis

Abstract

E-cadherin-p120 catenin complexes are essential for adherens junction (AJ) formation and for the maintenance of the normal epithelial phenotype. PLEKHA7 was originally identified as a member of this complex that tethers microtubules to the AJs and supports their overall integrity. Recently, we revealed that PLEKHA7 regulates cellular behavior via miRNAs by associating with the microprocessor complex at the apical zonula adherens (ZA). We have also identified a new set of PLEKHA7 interacting partners at the apical ZA, via proteomics. Our analysis shows that the main groups of proteins associating with PLEKHA7 are cytoskeletal-related and RNA-binding proteins. Here, we provide extended evidence for association of PLEKHA7 with several of these proteins. We also show that PLEKHA7 loss activates the actin regulator cofilin in a p120-dependent manner, providing an explanation for the effects of PLEKHA7 on the cortical actin ring. Interestingly, PLEKHA7 regulates the levels and associates with PP1α, a phosphatase responsible for cofilin activation. Finally, we clarify the mode of regulation of the oncogenic miR-19a by PLEKHA7. Overall, our findings support a multi-layered role of PLEKHA7 in converging cytoskeletal dynamics and miRNA-m...Continue Reading

References

Sep 12, 1995·Proceedings of the National Academy of Sciences of the United States of America·D L RimmJ S Morrow
Aug 10, 2000·The Journal of Cell Biology·N K NorenB Kreft
Sep 12, 2000·Nature Cell Biology·P Z AnastasiadisA B Reynolds
Oct 5, 2001·Nature Cell Biology·L A LigonE L Holzbaur
Nov 13, 2002·The Journal of Cell Biology·Renee C IretonAlbert B Reynolds
Dec 17, 2003·The Journal of Biological Chemistry·Masahiro YanagisawaPanos Z Anastasiadis
Nov 9, 2004·Nature·Richard I GregoryRamin Shiekhattar
Jun 10, 2005·Nature·Lin HeScott M Hammond
Feb 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Noora KotajaPaolo Sassone-Corsi
Jul 19, 2006·Molecular and Cellular Biology·Sonia GuilJavier F Cáceres
Jun 15, 2007·Nature Structural & Molecular Biology·Sonia Guil, Javier F Cáceres
Jan 19, 2008·Biochimica Et Biophysica Acta·Jun Miyoshi, Yoshimi Takai
Mar 8, 2008·FEBS Letters·E A Papakonstanti, C Stournaras
Aug 23, 2008·Cell Cycle·Shan DengLin Zhang
Nov 19, 2008·The Journal of Cell Biology·Edwin SotoPanos Z Anastasiadis
Feb 4, 2009·The Journal of Cell Biology·Michael R DohnAlbert B Reynolds
May 12, 2009·Nature Genetics·Daniel LevyCornelia M van Duijn
Sep 10, 2009·Current Topics in Developmental Biology·Tamako Nishimura, Masatoshi Takeichi
Dec 17, 2009·Genes & Development·Virginie OliveLin He
Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jakob LovénMarie Henriksson
Mar 17, 2010·The International Journal of Biochemistry & Cell Biology·Virginie OliveLin He
Dec 22, 2010·F1000 Biology Reports·James R Bamburg, Barbara W Bernstein
Jul 13, 2011·The Journal of Clinical Investigation·Ron C J SchackmannPatrick W B Derksen
Oct 28, 2011·Molecular Biology of the Cell·Andrew L SmithAlbert B Reynolds
Mar 14, 2013·Progress in Molecular Biology and Translational Science·Antonis KourtidisPanos Z Anastasiadis
Oct 2, 2013·Annual Review of Pathology·Gianpiero Di LevaCarlo M Croce
Aug 20, 2014·Proceedings of the National Academy of Sciences of the United States of America·Bradley T EndresAron M Geurts
Mar 4, 2015·Clinical & Experimental Ophthalmology·Ping ShuaiBo Gong
Aug 12, 2015·The Journal of Cell Biology·Chi-Shuo ChenSergey M Troyanovsky

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Citations

Apr 14, 2016·The International Journal of Biochemistry & Cell Biology·Jimit ShahSandra Citi
Sep 8, 2017·The Journal of Cell Biology·Antonis KourtidisPanos Z Anastasiadis
Jun 15, 2019·International Journal of Molecular Sciences·Amanda C DaulagalaAntonis Kourtidis
Apr 11, 2020·International Journal of Molecular Sciences·Joyce Nair-MenonAntonis Kourtidis
Jun 20, 2020·Biochimica Et Biophysica Acta. Biomembranes·Florian RouaudSandra Citi

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Methods Mentioned

BETA
GTPase
co-immunoprecipitation
co-IPs
confocal microscopy
immunoprecipitation
cross-linked proteomics
X-ray

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