title: srGAP2 arginine methylation regulates cell migration and cell spreading through promoting dimerization.
abstract: The Slit-Robo GTPase-activating proteins (srGAPs) are critical for neuronal migration through inactivation of Rho GTPases Cdc42, Rac1, and RhoA. Here we report that srGAP2 physically interacts with protein arginine methyltransferase 5 (PRMT5). srGAP2 localizes to the cytoplasm and plasma membrane protrusion. srGAP2 knockdown reduces cell adhesion spreading and increases cell migration, but has no effect on cell proliferation. PRMT5 binds to the N terminus of srGAP2 (225-538 aa) and methylates its C-terminal arginine residue Arg-927. The methylation mutant srGAP2-R927A fails to rescue the cell spreading rate, is unable to localize to the plasma membrane leading edge, and perturbs srGAP2 homodimer formation mediated by the F-BAR domain. These results suggest that srGAP2 arginine methylation plays important roles in cell spreading and cell migration through influencing membrane protrusion.
authors.affiliation: Key Laboratory of Molecular and Developmental Biology, Center for Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Shaoshi
authors.initials: S
authors.lastname: Guo
authors.forename: Shilai
authors.initials: S
authors.lastname: Bao
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001120:Arginine / Q000235:genetics / Q000378:metabolism; D016466:CHO Cells; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D006224:Cricetinae; D003412:Cricetulus; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008745:Methylation; D020125:Mutation, Missense; D011496:Protein Methyltransferases / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization / Q000502:physiology*; D011484:Protein-Arginine N-Methyltransferases; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D020690:GTPase-Activating Proteins; C107953:RAC1 protein, human; C501995:SRGAP2 protein, human; C066737:RHOA protein, human; D001120:Arginine; D011496:Protein Methyltransferases; C400529:PRMT5 protein, human; D011484:Protein-Arginine N-Methyltransferases; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein
references.citation: Nat Cell Biol. 2002 Apr;4(4):E97-100
references.pmid: 11944043
references.citation: PLoS One. 2008 Jan 23;3(1):e1477
references.pmid: 18213385
references.citation: J Biol Chem. 2003 Mar 7;278(10):8452-9
references.pmid: 12482861
references.citation: Curr Biol. 1997 Jul 1;7(7):479-87
references.pmid: 9210375
references.citation: Science. 2004 Jan 23;303(5657):495-9
references.pmid: 14645856
references.citation: Cell Res. 2010 Sep;20(9):1023-33
references.pmid: 20421892
references.citation: Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19788-93
references.pmid: 17172447
references.citation: J Cell Biol. 1998 Nov 30;143(5):1385-98
references.pmid: 9832565
references.citation: Proc Natl Acad Sci U S A. 2007 May 8;104(19):7939-44
references.pmid: 17483462
references.citation: Dev Cell. 2005 Dec;9(6):791-804
references.pmid: 16326391
references.citation: Structure. 2007 Jul;15(7):839-52
references.pmid: 17540576
references.citation: Exp Cell Res. 2006 Jul 15;312(12):2379-93
references.pmid: 16730001
references.citation: J Biol Chem. 1959 Mar;234(3):603-8
references.pmid: 13641268
references.citation: J Biol Chem. 2010 Apr 23;285(17):12695-705
references.pmid: 20159986
references.citation: Nat Struct Mol Biol. 2009 Mar;16(3):304-311
references.pmid: 19234465
references.citation: Mol Cell Biol. 2009 Apr;29(7):1909-21
references.pmid: 19188441
references.citation: Oncogene. 2004 Jul 22;23(33):5586-93
references.pmid: 15184880
references.citation: Trends Genet. 1994 Dec;10(12):436-40
references.pmid: 7871593
references.citation: Mol Cell Biol. 2004 Nov;24(21):9630-45
references.pmid: 15485929
references.citation: Nat Cell Biol. 2006 Jun;8(6):623-30
references.pmid: 16699504
references.citation: J Cell Biol. 2006 Jan 16;172(2):269-79
references.pmid: 16418535
references.citation: Mol Cell. 2003 Apr;11(4):1055-66
references.pmid: 12718890
references.citation: Cell. 2001 Oct 19;107(2):209-21
references.pmid: 11672528
references.citation: J Biochem. 1996 Aug;120(2):215-28
references.pmid: 8889802
references.citation: Annu Rev Cell Dev Biol. 2005;21:247-69
references.pmid: 16212495
references.citation: Structure. 2007 Jul;15(7):751-3
references.pmid: 17637334
references.citation: Science. 2003 Dec 5;302(5651):1704-9
references.pmid: 14657486
references.citation: Nat Cell Biol. 2008 Dec;10(12):1431-9
references.pmid: 19011621
references.citation: Cell. 1996 Feb 9;84(3):359-69
references.pmid: 8608589
references.citation: Cell. 2007 May 18;129(4):761-72
references.pmid: 17512409
references.citation: J Biol Chem. 2008 Jul 18;283(29):20454-72
references.pmid: 18448434
references.citation: J Biol Chem. 2001 Apr 6;276(14):11393-401
references.pmid: 11152681
references.citation: Biochem J. 2003 Apr 15;371(Pt 2):463-71
references.pmid: 12570871
references.citation: Cell. 2008 Mar 7;132(5):807-17
references.pmid: 18329367
references.citation: J Biol Chem. 2006 Nov 17;281(46):35347-58
references.pmid: 17003044
references.citation: J Biol Chem. 1999 May 7;274(19):13198-204
references.pmid: 10224076
references.citation: J Cell Biol. 2007 Mar 26;176(7):953-64
references.pmid: 17371834
references.citation: J Biol Chem. 2004 Apr 9;279(15):14929-36
references.pmid: 14752106
references.citation: Curr Biol. 2006 Jun 6;16(11):1077-89
references.pmid: 16753561
references.citation: Cell. 2008 Oct 31;135(3):497-509
references.pmid: 18984161
references.citation: J Cell Sci. 2001 May;114(Pt 10):1801-9
references.pmid: 11329366
references.citation: Cell. 2009 Sep 4;138(5):990-1004
references.pmid: 19737524
references.citation: Biochem Soc Trans. 2005 Nov;33(Pt 5):891-5
references.pmid: 16246005