title: PLEKHA7 defines an apical junctional complex with cytoskeletal associations and miRNA-mediated growth implications.
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-mediated growth regulation at the ZA, with potentially critical implications in cancer that warrant further investigation.
authors.affiliation: a Department of Cancer Biology , Mayo Clinic Comprehensive Cancer, Center, Mayo Clinic , Jacksonville , FL , USA.
authors.forename: Antonis
authors.initials: A
authors.lastname: Kourtidis
authors.affiliation: a Department of Cancer Biology , Mayo Clinic Comprehensive Cancer, Center, Mayo Clinic , Jacksonville , FL , USA.
authors.forename: Panos Z
authors.initials: PZ
authors.lastname: Anastasiadis
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D051177:Catenins / Q000235:genetics / Q000378:metabolism; D051338:Cofilin 1 / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D022001:Focal Adhesions / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008870:Microtubules / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000095002:Delta Catenin
chemical_list: D000199:Actins; D015820:Cadherins; D002352:Carrier Proteins; D051177:Catenins; D051338:Cofilin 1; D003598:Cytoskeletal Proteins; C549214:MIRN19A microRNA, human; D035683:MicroRNAs; C533786:PLEKHA7 protein, human; D016601:RNA-Binding Proteins; D000095002:Delta Catenin; C000722347:CTNND1 protein, human
keywords: E-cadherin; PLEKHA7; actin; adherens junctions; cell growth; miR-19a; miRNAs; microprocessor; p120 catenin; zonula adherens
references.citation: Sci Rep. 2015 Aug 25;5:13350
references.pmid: 26302825
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1553-8
references.pmid: 20080637
references.citation: J Biol Chem. 2004 Mar 5;279(10 ):9512-21
references.pmid: 14676216
references.citation: Cell. 2014 Feb 27;156(5):893-906
references.pmid: 24581491
references.citation: Cell. 2006 Dec 1;127(5):1027-39
references.pmid: 17129786
references.citation: J Cell Biol. 2008 Nov 17;183(4):737-49
references.pmid: 19015320
references.citation: Nat Cell Biol. 2015 Sep;17(9):1145-57
references.pmid: 26302406
references.citation: Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8813-7
references.pmid: 7568023
references.citation: Mol Biol Cell. 2004 Apr;15(4):1580-90
references.pmid: 14718566
references.citation: Mol Biol Cell. 2012 Jan;23 (1):99-110
references.pmid: 22031287
references.citation: Nature. 2005 Jun 9;435(7043):828-33
references.pmid: 15944707
references.citation: Genes Dev. 2012 Jan 1;26(1):69-81
references.pmid: 22215812
references.citation: J Cell Biol. 2000 Aug 7;150(3):567-80
references.pmid: 10931868
references.citation: Hybridoma. 1998 Apr;17(2):175-83
references.pmid: 9627058
references.citation: Cell Growth Differ. 1999 Dec;10(12):839-54
references.pmid: 10616909
references.citation: Annu Rev Pathol. 2014;9:287-314
references.pmid: 24079833
references.citation: PLoS One. 2012;7(12):e51442
references.pmid: 23251535
references.citation: Nat Genet. 2009 Jun;41(6):677-87
references.pmid: 19430479
references.citation: F1000 Biol Rep. 2010 Aug 19;2:62
references.pmid: 21173851
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2647-52
references.pmid: 16477042
references.citation: J Cell Biol. 2009 Feb 9;184(3):437-50
references.pmid: 19188496
references.citation: Int J Biochem Cell Biol. 2010 Aug;42(8):1348-54
references.pmid: 20227518
references.citation: J Cell Biol. 2003 Nov 10;163(3):547-57
references.pmid: 14610057
references.citation: Science. 2014 Oct 31;346(6209):1254211
references.pmid: 25359979
references.citation: Nat Cell Biol. 2007 May;9(5):604-11
references.pmid: 17435748
references.citation: J Cell Biol. 2002 Nov 11;159(3):465-76
references.pmid: 12427869
references.citation: Prog Mol Biol Transl Sci. 2013;116:409-32
references.pmid: 23481205
references.citation: Mol Cell Biol. 2006 Aug;26(15):5744-58
references.pmid: 16847328
references.citation: J Clin Invest. 2011 Aug;121(8):3176-88
references.pmid: 21747168
references.citation: Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):12817-22
references.pmid: 25136115
references.citation: Cell. 2008 Nov 28;135(5):948-59
references.pmid: 19041755
references.citation: Nat Cell Biol. 2001 Oct;3(10 ):913-7
references.pmid: 11584273
references.citation: Cell. 2000 Jan 21;100(2):209-19
references.pmid: 10660044
references.citation: Invest Ophthalmol Vis Sci. 2014 May 06;55(6):3833-41
references.pmid: 24801512
references.citation: PLoS One. 2015 Aug 13;10(8):e0135442
references.pmid: 26270346
references.citation: Mol Biol Cell. 2005 Apr;16(4):1938-47
references.pmid: 15703215
references.citation: Nat Cell Biol. 2000 Sep;2(9):637-44
references.pmid: 10980705
references.citation: Cell. 2001 Feb 23;104(4):605-17
references.pmid: 11239416
references.citation: FEBS Lett. 2008 Jun 18;582(14):2120-7
references.pmid: 18325339
references.citation: J Cell Biol. 2015 Aug 17;210(4):647-61
references.pmid: 26261181
references.citation: Nat Struct Mol Biol. 2007 Jul;14(7):591-6
references.pmid: 17558416
references.citation: J Cell Sci. 2001 Feb;114(Pt 4):695-707
references.pmid: 11171375
references.citation: Genes Dev. 2009 Dec 15;23(24):2839-49
references.pmid: 20008935
references.citation: Oncogene. 2010 Nov 25;29(47):6233-44
references.pmid: 20729910
references.citation: Eur J Immunol. 2000 Dec;30(12):3422-31
references.pmid: 11093160
references.citation: PLoS One. 2010 Aug 20;5(8):e12207
references.pmid: 20808826
references.citation: Biochim Biophys Acta. 2008 Mar;1778(3):670-91
references.pmid: 18201548
references.citation: Curr Top Dev Biol. 2009;89:33-54
references.pmid: 19737641
references.citation: Nature. 2004 Nov 11;432(7014):235-40
references.pmid: 15531877
references.citation: Clin Exp Ophthalmol. 2015 Aug;43(6):523-30
references.pmid: 25732101
references.citation: Cell Cycle. 2008 Sep 1;7(17):2643-6
references.pmid: 18719391