title: ERK7 regulates ciliogenesis by phosphorylating the actin regulator CapZIP in cooperation with Dishevelled.
abstract: Cilia are essential for embryogenesis and maintenance of homeostasis, but little is known about the signalling pathways that regulate ciliogenesis. Here, we identify ERK7, an atypical mitogen-activated protein kinase, as a key regulator of ciliogenesis. ERK7 is strongly expressed in ciliated tissues of Xenopus embryos. ERK7 knockdown markedly diminishes both the number and the length of cilia in multiciliated cells, and it inhibits the apical migration of basal bodies. Moreover, ERK7 knockdown results in a loss of the apical actin meshwork, which is required for the proper migration of basal bodies. We find that the actin regulator CapZIP, which has been shown to regulate ciliogenesis in a phosphorylation-dependent manner, is an ERK7 substrate, and that Dishevelled, which has also been shown to regulate ciliogenesis, facilitates ERK7 phosphorylation of CapZIP through binding to both ERK7 and CapZIP. Collectively, these results identify an ERK7/Dishevelled/CapZIP axis that regulates ciliogenesis.
authors.affiliation: Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Miyatake
authors.affiliation: Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Morioh
authors.initials: M
authors.lastname: Kusakabe
authors.affiliation: Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Takahashi
authors.affiliation: Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Nishida
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D064652:Basal Bodies / Q000378:metabolism; D001483:Base Sequence; D002923:Cilia / Q000235:genetics* / Q000378:metabolism; D000072261:Dishevelled Proteins; D004625:Embryo, Nonmammalian; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism*; D029867:Xenopus Proteins / Q000235:genetics* / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; C000606098:RCSD1 protein, Xenopus; D012333:RNA, Messenger; D029867:Xenopus Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D048052:Mitogen-Activated Protein Kinase 3
references.citation: J Biol Chem. 2001 Jun 15;276(24):21272-9
references.pmid: 11287416
references.citation: Nat Cell Biol. 2010 Apr;12(4):407-12
references.pmid: 20305649
references.citation: Cell Rep. 2012 May 31;1(5):516-27
references.pmid: 22832275
references.citation: Dev Cell. 2014 Jan 13;28(1):70-80
references.pmid: 24434137
references.citation: Development. 2014 Apr;141(7):1514-25
references.pmid: 24598166
references.citation: Cell Signal. 2010 May;22(5):717-27
references.pmid: 20006983
references.citation: Nat Genet. 2008 Dec;40(12):1454-60
references.pmid: 19011629
references.citation: Dev Biol. 1993 Dec;160(2):355-68
references.pmid: 8253269
references.citation: J Cell Biol. 2011 Oct 3;195(1):19-26
references.pmid: 21949415
references.citation: CSH Protoc. 2008 Feb 01;2008:pdb.prot4957
references.pmid: 21356778
references.citation: Genes Cells. 2007 Aug;12 (8):961-7
references.pmid: 17663724
references.citation: Biochem J. 2005 Jul 1;389(Pt 1):127-35
references.pmid: 15850461
references.citation: Dev Biol. 2007 Dec 1;312(1):115-30
references.pmid: 17961536
references.citation: Nat Genet. 2006 Nov;38(11):1316-22
references.pmid: 17013396
references.citation: Nat Rev Genet. 2010 May;11(5):331-44
references.pmid: 20395968
references.citation: Development. 2001 Jul;128(13):2581-92
references.pmid: 11493574
references.citation: Dis Model Mech. 2011 Mar;4(2):179-92
references.pmid: 21183475
references.citation: Mech Dev. 2000 Jan;90(1):41-51
references.pmid: 10585561
references.citation: Nat Cell Biol. 2010 Feb;12 (2):170-6
references.pmid: 20098415
references.citation: Am J Physiol Lung Cell Mol Physiol. 2002 Dec;283(6):L1315-21
references.pmid: 12388377
references.citation: Nature. 2010 Jul 15;466(7304):378-82
references.pmid: 20562861
references.citation: Trends Genet. 1999 Aug;15(8):314-9
references.pmid: 10431193
references.citation: Oncogene. 2007 May 14;26(22):3100-12
references.pmid: 17496909
references.citation: Nat Rev Mol Cell Biol. 2007 Nov;8(11):880-93
references.pmid: 17955020
references.citation: PLoS One. 2010 Feb 02;5(2):e8999
references.pmid: 20126399
references.citation: Nature. 2002 Jul 4;418(6893):37-8
references.pmid: 12097899
references.citation: Development. 2014 Apr;141(7):1526-33
references.pmid: 24598162
references.citation: Autophagy. 2012 Dec;8(12 ):1724-40
references.pmid: 22948227
references.citation: Curr Biol. 2007 Jan 9;17(1):60-6
references.pmid: 17208188
references.citation: Dev Biol. 2009 Jul 15;331(2):281-91
references.pmid: 19450574
references.citation: Nat Genet. 2008 Dec;40(12):1445-53
references.pmid: 19011630
references.citation: EMBO J. 2011 Aug 16;30(18):3684-700
references.pmid: 21847093
references.citation: Development. 2012 Feb;139(3):514-24
references.pmid: 22190638
references.citation: Dev Genes Evol. 2004 Apr;214(4):200-5
references.pmid: 14986136
references.citation: Methods Enzymol. 2013;525:285-309
references.pmid: 23522475
references.citation: Development. 1999 Nov;126(21):4715-28
references.pmid: 10518489
references.citation: Nature. 2013 Dec 19;504(7480):456-9
references.pmid: 24226769
references.citation: Nat Genet. 2008 Jul;40(7):871-9
references.pmid: 18552847
references.citation: Differentiation. 2007 Feb;75(2):133-46
references.pmid: 17316383
references.citation: Biochim Biophys Acta. 2007 Aug;1773(8):1376-87
references.pmid: 17161475
references.citation: Development. 2011 Feb;138(4):705-14
references.pmid: 21266406
references.citation: Biochem J. 2006 Feb 15;394(Pt 1):365-73
references.pmid: 16336213
references.citation: Genes Cells. 2006 Feb;11(2):177-91
references.pmid: 16436054
references.citation: Semin Cell Dev Biol. 2009 Jun;20(4):464-71
references.pmid: 19056505
references.citation: Nat Cell Biol. 2012 Jan 08;14(2):140-7
references.pmid: 22231168
references.citation: Nat Genet. 2006 Mar;38(3):303-11
references.pmid: 16493421
references.citation: Curr Biol. 1996 Nov 1;6(11):1456-67
references.pmid: 8939601
references.citation: J Cell Biol. 2010 Aug 23;190(4):575-86
references.pmid: 20733054
references.citation: Methods Mol Biol. 2013;945:123-43
references.pmid: 23097105
references.citation: Nat Rev Mol Cell Biol. 2011 Apr;12(4):222-34
references.pmid: 21427764