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Regulated mesoderm migration is necessary for the proper morphogenesis and organ formation during embryonic development. Cell migration and its dependence on the cytoskeleton and signaling machines have been studied extensively in cultured cells; in contrast, remarkably little is known about the mechanisms that regulate mesoderm cell migration in vivo. Here, we report the identification and characterization of a mouse mutation in striatin-interacting protein 1 ( Strip1 ) that disrupts migration of the mesoderm after the gastrulation epithelial-to-mesenchymal transition (EMT). STRIP1 is a core component of the biochemically defined mammalian striatin-interacting phosphatases and kinase (STRIPAK) complexes that appear to act through regulation of protein phosphatase 2A (PP2A), but their functions in mammals in vivo have not been examined. Strip1 -null mutants arrest development at midgestation with profound disruptions in the organization of the mesoderm and its derivatives, including a complete failure of the anterior extension of axial mesoderm. Analysis of cultured mesoderm explants and mouse embryonic fibroblasts from null mutants shows that the mesoderm migration defect is correlated with decreased cell spreading, abnormal focal adhesions, changes in the organization of the actin cytoskeleton, and decreased velocity of cell migration. The results show that STRIPAK complexes are essential for cell migration and tissue morphogenesis in vivo.

Competing Interests: The authors declare no conflict of interest.

Titel:	STRIP1, a core component of STRIPAK complexes, is essential for normal mesoderm migration in the mouse embryo.
Autor/in / Beteiligte Person:	Bazzi, H ; Soroka, E ; Alcorn, HL ; Anderson, KV
Zeitschrift:	Proceedings of the National Academy of Sciences of the United States of America, Jg. 114 (2017-12-19), Heft 51, S. E10928-E10936
Veröffentlichung:	Washington, DC : National Academy of Sciences, 2017
Medientyp:	academicJournal
ISSN:	1091-6490 (electronic)
DOI:	10.1073/pnas.1713535114
Schlagwort:	Actins metabolism Animals Carrier Proteins genetics Cell Movement Mesoderm cytology Mesoderm embryology Mice Morphogenesis genetics Mutation Phenotype Carrier Proteins metabolism Embryonic Development genetics Mesoderm metabolism Multiprotein Complexes metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Language: English [Proc Natl Acad Sci U S A] 2017 Dec 19; Vol. 114 (51), pp. E10928-E10936. <i>Date of Electronic Publication: </i>2017 Dec 04. MeSH Terms: Embryonic Development* / genetics ; Carrier Proteins / metabolism ; Mesoderm / metabolism ; Multiprotein Complexes / *metabolism ; Actins / metabolism ; Animals ; Carrier Proteins / genetics ; Cell Movement ; Mesoderm / cytology ; Mesoderm / embryology ; Mice ; Morphogenesis / genetics ; Mutation ; Phenotype References: Dev Cell. 2014 Dec 8;31(5):572-85. (PMID: 25490267) ; Mol Cell. 2009 Mar 13;33(5):537-45. (PMID: 19285938) ; Dev Cell. 2008 Oct;15(4):509-20. (PMID: 18854136) ; Development. 2009 Jun;136(12):2039-48. (PMID: 19439496) ; FEBS J. 2016 Mar;283(6):1004-24. (PMID: 26507691) ; Biol Open. 2017 Jun 15;6(6):752-764. (PMID: 28619992) ; MethodsX. 2014 Jul 07;1:56-9. (PMID: 26150935) ; Dev Dyn. 2016 May;245(5):547-57. (PMID: 26845388) ; Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):5913-9. (PMID: 15755804) ; Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12370-5. (PMID: 9770493) ; Nature. 2016 Sep 22;537(7621):508-514. (PMID: 27626380) ; Curr Opin Genet Dev. 2009 Aug;19(4):343-9. (PMID: 19647425) ; Cell. 2011 Aug 5;146(3):488-488.e2. (PMID: 21816280) ; Dev Biol. 1967 Dec;16(6):564-76. (PMID: 5584563) ; Nat Cell Biol. 2016 Dec;18(12 ):1281-1291. (PMID: 27870829) ; Development. 2011 Jul;138(14):3011-20. (PMID: 21693517) ; PLoS Genet. 2015 Oct 23;11(10):e1005551. (PMID: 26496195) ; BMC Biol. 2011 Aug 11;9:54. (PMID: 21834987) ; Nature. 2015 Mar 26;519(7544):425-30. (PMID: 25799996) ; Genesis. 2004 Mar;38(3):151-8. (PMID: 15048813) ; Development. 2007 Jun;134(11):2007-16. (PMID: 17507402) ; Oncogene. 2016 Sep 1;35(35):4549-57. (PMID: 26876214) ; Int J Biochem Cell Biol. 2014 Feb;47:118-48. (PMID: 24333164) ; Biochem Biophys Res Commun. 1997 Aug 18;237(2):318-24. (PMID: 9268708) ; Nature. 2003 Nov 6;426(6962):83-7. (PMID: 14603322) ; Development. 1999 Nov;126(21):4691-701. (PMID: 10518487) ; Philos Trans R Soc Lond B Biol Sci. 2000 Jul 29;355(1399):897-922. (PMID: 11128984) ; Nat Commun. 2016 Apr 28;7:11317. (PMID: 27122098) ; Development. 2006 Aug;133(16):3075-83. (PMID: 16831833) ; J Biol Chem. 2012 Jul 20;287(30):25019-29. (PMID: 22665485) ; Mech Dev. 2002 Dec;119 Suppl 1:S97-S101. (PMID: 14516668) ; Genetics. 2012 Apr;190(4):1325-39. (PMID: 22298706) ; Development. 2001 May;128(9):1559-72. (PMID: 11290295) ; BMC Biochem. 2011 Oct 10;12:54. (PMID: 21985334) ; Dev Cell. 2011 Sep 13;21(3):546-58. (PMID: 21920318) ; Genetics. 1960 Nov;45(11):1531-8. (PMID: 17248016) ; Nature. 2011 Jun 15;474(7351):337-42. (PMID: 21677750) ; J Cell Biol. 1996 Aug;134(4):1051-62. (PMID: 8769426) ; Dev Cell. 2001 Jul;1(1):37-49. (PMID: 11703922) ; Mol Cell Biol. 2003 Mar;23(5):1750-63. (PMID: 12588993) ; Genes Genet Syst. 2014;89(3):109-20. (PMID: 25475934) ; Genetics. 2002 Jan;160(1):169-80. (PMID: 11805054) ; J Biol Chem. 2000 Feb 25;275(8):5257-63. (PMID: 10681496) ; Cell Death Dis. 2014 Jul 10;5:e1320. (PMID: 25010986) ; Development. 2016 Sep 1;143(17 ):3097-108. (PMID: 27510976) ; Nat Genet. 2000 Jun;25(2):139-40. (PMID: 10835623) ; Cold Spring Harb Perspect Biol. 2014 Jun 26;7(11):null. (PMID: 24968703) ; Eukaryot Cell. 2011 Aug;10(8):1100-9. (PMID: 21666072) ; Mol Cell Proteomics. 2009 Jan;8(1):157-71. (PMID: 18782753) ; Nat Cell Biol. 2014 Dec;16(12):1146-56. (PMID: 25419850) ; J Biol Chem. 2013 Jun 7;288(23):16986-97. (PMID: 23625923) ; Development. 1993 Jul;118(3):829-44. (PMID: 7521282) ; Nat Cell Biol. 2015 Jan;17 (1):68-80. (PMID: 25531779) ; J Embryol Exp Morphol. 1974 Dec;32(3):723-8. (PMID: 4463226) ; Dev Cell. 2007 Dec;13(6):884-96. (PMID: 18061569) ; Genesis. 2012 May;50(5):429-36. (PMID: 21998041) ; Dev Biol. 2000 Nov 15;227(2):648-60. (PMID: 11071781) Grant Information: P30 CA008748 United States CA NCI NIH HHS; R01 HD035455 United States HD NICHD NIH HHS; R37 HD035455 United States HD NICHD NIH HHS Contributed Indexing: Keywords: PP2A; STRIP1; STRIPAK; cell migration; mouse embryo Substance Nomenclature: 0 (Actins) ; 0 (Carrier Proteins) ; 0 (Multiprotein Complexes) Entry Date(s): Date Created: 20171206 Date Completed: 20180702 Latest Revision: 20181113 Update Code: 20240513 PubMed Central ID: PMC5754794

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STRIP1, a core component of STRIPAK complexes, is essential for normal mesoderm migration in the mouse embryo.