title: Bringing KASH under the SUN: the many faces of nucleo-cytoskeletal connections.
abstract: The nucleus is the most prominent cellular organelle, and its sharp boundaries suggest the compartmentalization of the nucleoplasm from the cytoplasm. However, the recent identification of evolutionarily conserved linkers of the nucleoskeleton to the cytoskeleton (LINC) complexes, a family of macromolecular assemblies that span the double membrane of the nuclear envelope, reveals tight physical connections between the two compartments. Here, we review the structure and evolutionary conservation of SUN and KASH domain-containing proteins, whose interaction within the perinuclear space forms the "nuts and bolts" of LINC complexes. Moreover, we discuss the function of these complexes in nuclear, centrosomal, and chromosome dynamics, and their connection to human disease.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: David
authors.initials: D
authors.lastname: Razafsky
authors.forename: Didier
authors.initials: D
authors.lastname: Hodzic
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D019143:Evolution, Molecular; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D008565:Membrane Proteins; D046912:Multiprotein Complexes
references.citation: Cell Mol Life Sci. 2009 May;66(9):1518-33
references.pmid: 19125221
references.citation: Science. 2002 Oct 11;298(5592):406-9
references.pmid: 12169658
references.citation: Nat Genet. 2007 Jan;39(1):80-5
references.pmid: 17159980
references.citation: Biophys J. 2008 Dec;95(11):5462-75
references.pmid: 18790843
references.citation: Proc Natl Acad Sci U S A. 2007 May 1;104(18):7426-31
references.pmid: 17452644
references.citation: J Cell Biol. 2009 Jul 27;186(2):229-41
references.pmid: 19635841
references.citation: Development. 1999 Jun;126(14):3171-81
references.pmid: 10375507
references.citation: J Cell Sci. 2004 Sep 15;117(Pt 20):4779-86
references.pmid: 15331638
references.citation: Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14819-24
references.pmid: 17785424
references.citation: Cell. 2003 Dec 26;115(7):825-36
references.pmid: 14697201
references.citation: Genes Dev. 2006 Jun 1;20(11):1384-93
references.pmid: 16751177
references.citation: Cell. 2008 Jun 27;133(7):1188-201
references.pmid: 18585353
references.citation: BMC Cell Biol. 2006 Oct 24;7:38
references.pmid: 17062158
references.citation: J Cell Biol. 1995 Jul;130(1):15-27
references.pmid: 7790369
references.citation: J Cell Biol. 2006 Jan 2;172(1):41-53
references.pmid: 16380439
references.citation: J Clin Invest. 2004 Feb;113(3):349-51
references.pmid: 14755330
references.citation: Mol Biol Cell. 2006 Apr;17(4):1790-801
references.pmid: 16481402
references.citation: J Biol Chem. 2004 Jun 11;279(24):25805-12
references.pmid: 15082709
references.citation: J Cell Sci. 2008 Oct 15;121(Pt 20):3476-86
references.pmid: 18827015
references.citation: J Cell Sci. 2005 Aug 1;118(Pt 15):3419-30
references.pmid: 16079285
references.citation: Mol Cell Proteomics. 2002 Jul;1(7):517-27
references.pmid: 12239280
references.citation: J Biol Chem. 2000 Feb 18;275(7):4840-7
references.pmid: 10671519
references.citation: Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4359-64
references.pmid: 15749817
references.citation: J Cell Biol. 1995 May;129(4):1033-47
references.pmid: 7744953
references.citation: Neuron. 2005 May 5;46(3):383-8
references.pmid: 15882636
references.citation: Mol Biol Cell. 2005 Jul;16(7):3411-24
references.pmid: 15843432
references.citation: Cell. 1993 Jul 2;73(7):1267-79
references.pmid: 8324822
references.citation: J Neurosci. 1995 Feb;15(2):981-9
references.pmid: 7869123
references.citation: J Cell Biol. 1995 Feb;128(3):355-61
references.pmid: 7844149
references.citation: J Cell Biol. 2005 Dec 5;171(5):799-810
references.pmid: 16330710
references.citation: Development. 2009 Aug;136(16):2725-33
references.pmid: 19605495
references.citation: Novartis Found Symp. 2005;264:81-90; discussion 90-97, 227-30
references.pmid: 15773749
references.citation: Mol Biol Cell. 1999 Jul;10(7):2393-406
references.pmid: 10397772
references.citation: Cell. 2008 Sep 19;134(6):1055-65
references.pmid: 18805097
references.citation: Plant Cell. 2005 Feb;17(2):389-403
references.pmid: 15659629
references.citation: Mech Dev. 1996 Nov;60(1):83-94
references.pmid: 9025063
references.citation: Am J Hum Genet. 2002 Mar;70(3):726-36
references.pmid: 11799477
references.citation: Curr Opin Genet Dev. 2003 Jun;13(3):223-30
references.pmid: 12787783
references.citation: Nat Rev Mol Cell Biol. 2001 Aug;2(8):621-7
references.pmid: 11483995
references.citation: J Clin Invest. 2004 Feb;113(3):370-8
references.pmid: 14755334
references.citation: Mol Biol Cell. 2002 Mar;13(3):892-901
references.pmid: 11907270
references.citation: Proc Natl Acad Sci U S A. 2004 May 4;101(18):6987-92
references.pmid: 15100407
references.citation: Exp Cell Res. 2008 May 1;314(8):1892-905
references.pmid: 18396275
references.citation: Development. 2004 Oct;131(19):4677-86
references.pmid: 15329347
references.citation: Proc Natl Acad Sci U S A. 1988 Nov;85(22):8531-4
references.pmid: 2847165
references.citation: J Struct Biol. 2000 Apr;129(2-3):313-23
references.pmid: 10806082
references.citation: Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):849-54
references.pmid: 9023345
references.citation: J Cell Biol. 1997 Jun 2;137(5):1001-16
references.pmid: 9166402
references.citation: Mol Biol Cell. 2005 Mar;16(3):1406-16
references.pmid: 15647372
references.citation: Nat Rev Mol Cell Biol. 2002 Aug;3(8):575-85
references.pmid: 12154369
references.citation: J Biol Chem. 2000 Oct 13;275(41):31986-95
references.pmid: 10878022
references.citation: Cell. 2007 Jan 12;128(1):29-43
references.pmid: 17218253
references.citation: Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai). 2003 Mar;35(3):283-8
references.pmid: 12621555
references.citation: Proc Natl Acad Sci U S A. 2009 Jun 23;106(25):10207-12
references.pmid: 19509342
references.citation: Nat Neurosci. 2004 Nov;7(11):1169-70
references.pmid: 15508010
references.citation: J Cell Biol. 2007 Dec 3;179(5):845-54
references.pmid: 18039933
references.citation: Nat Rev Mol Cell Biol. 2009 Jan;10(1):75-82
references.pmid: 19197334
references.citation: Development. 1997 Apr;124(8):1497-507
references.pmid: 9108366
references.citation: Nat Rev Mol Cell Biol. 2006 Oct;7(10):782-8
references.pmid: 16926857
references.citation: Cell. 1998 Feb 20;92(4):547-57
references.pmid: 9491895
references.citation: Hum Mol Genet. 2005 Jan 1;14(1):155-69
references.pmid: 15548545
references.citation: J Cell Biol. 2007 Aug 27;178(5):785-98
references.pmid: 17724119
references.citation: J Cell Sci. 2005 Feb 15;118(Pt 4):673-87
references.pmid: 15671068
references.citation: Mol Genet Metab. 2006 Apr;87(4):289-302
references.pmid: 16364671
references.citation: Cell Mol Life Sci. 2001 Nov;58(12-13):1748-57
references.pmid: 11766876
references.citation: Hum Mol Genet. 2004 Nov 1;13(21):2567-80
references.pmid: 15367494
references.citation: Neuron. 2004 Oct 14;44(2):263-77
references.pmid: 15473966
references.citation: J Cell Biol. 2004 Jun 7;165(5):709-21
references.pmid: 15173193
references.citation: Mol Biol Cell. 2000 Nov;11(11):3937-47
references.pmid: 11071918
references.citation: Nat Genet. 1994 Dec;8(4):323-7
references.pmid: 7894480
references.citation: Mol Cell Biol. 2006 May;26(10):3738-51
references.pmid: 16648470
references.citation: J Mol Biol. 2009 Mar 13;386(5):1392-402
references.pmid: 19109977
references.citation: Proc Natl Acad Sci U S A. 2006 Sep 5;103(36):13397-402
references.pmid: 16938876
references.citation: Annu Rev Neurosci. 2005;28:223-50
references.pmid: 16022595
references.citation: Science. 2003 Sep 5;301(5638):1380-2
references.pmid: 12958361
references.citation: J Biol Chem. 2004 Oct 15;279(42):43462-7
references.pmid: 15292200
references.citation: FEBS Lett. 2002 Feb 20;513(1):119-23
references.pmid: 11911890
references.citation: Fly (Austin). 2008 Mar-Apr;2(2):74-81
references.pmid: 18820482
references.citation: J Cell Sci. 2002 Aug 1;115(Pt 15):3207-22
references.pmid: 12118075
references.citation: Hum Mol Genet. 2009 Feb 15;18(4):607-20
references.pmid: 19008300
references.citation: J Cell Sci. 2006 Dec 15;119(Pt 24):5021-9
references.pmid: 17158909
references.citation: Cell. 2008 Aug 8;134(3):427-38
references.pmid: 18692466
references.citation: J Cell Sci. 2002 Jan 1;115(Pt 1):61-70
references.pmid: 11801724
references.citation: Nat Rev Mol Cell Biol. 2007 May;8(5):414-20
references.pmid: 17440484
references.citation: Biophys J. 2007 Oct 1;93(7):2542-52
references.pmid: 17631533
references.citation: Cell Tissue Res. 2004 Feb;315(2):279-83
references.pmid: 14614621
references.citation: Cell. 2006 Apr 7;125(1):59-69
references.pmid: 16615890
references.citation: J Cell Biochem. 2000 Apr;77(4):584-95
references.pmid: 10771514
references.citation: Fly (Austin). 2007 Mar-Apr;1(2):75-85
references.pmid: 18820457
references.citation: Dev Biol. 2006 Jan 15;289(2):336-45
references.pmid: 16337624
references.citation: J Cell Biol. 2006 Aug 28;174(5):665-75
references.pmid: 16923827
references.citation: Mol Biol Cell. 2009 Jun;20(11):2661-72
references.pmid: 19339278
references.citation: Brain Res. 2008 Feb 4;1192:29-36
references.pmid: 17560964
references.citation: J Physiol. 2003 Sep 1;551(Pt 2):467-78
references.pmid: 12813146
references.citation: Bioessays. 2005 Nov;27(11):1136-46
references.pmid: 16237665
references.citation: Cell Mol Life Sci. 2001 Nov;58(12-13):1741-7
references.pmid: 11766875
references.citation: Curr Biol. 1999 Nov 4;9(21):1211-20
references.pmid: 10556085
references.citation: Exp Cell Res. 2004 May 1;295(2):330-9
references.pmid: 15093733
references.citation: J Cell Sci. 2007 Oct 1;120(Pt 19):3384-94
references.pmid: 17881500
references.citation: Expert Rev Mol Med. 2005 Jun 13;7(11):1-15
references.pmid: 15953398
references.citation: Development. 1994 Sep;120(9):2609-18
references.pmid: 7956836
references.citation: Genomics. 2002 Nov;80(5):473-81
references.pmid: 12408964
references.citation: Mol Genet Genomics. 2004 Jan;270(6):449-61
references.pmid: 14655046
references.citation: J Cell Biol. 2000 Mar 20;148(6):1097-101
references.pmid: 10725321
references.citation: J Cell Biol. 2001 Mar 5;152(5):923-34
references.pmid: 11238449
references.citation: DNA Cell Biol. 2006 Oct;25(10):554-62
references.pmid: 17132086
references.citation: J Cell Biol. 1999 Nov 29;147(5):913-20
references.pmid: 10579712
references.citation: J Cell Sci. 2008 Jun 1;121(11):1887-98
references.pmid: 18477613
references.citation: Nat Neurosci. 2004 Nov;7(11):1195-203
references.pmid: 15475953
references.citation: J Clin Invest. 2009 Jul;119(7):1825-36
references.pmid: 19587457
references.citation: J Cell Sci. 2004 Feb 1;117(Pt 4):619-29
references.pmid: 14709720
references.citation: FEBS Lett. 2000 Jul 7;476(3):124-8
references.pmid: 10913598
references.citation: J Cell Sci. 2004 Mar 1;117(Pt 7):979-87
references.pmid: 14996929
references.citation: Fly (Austin). 2008 Mar-Apr;2(2):82-91
references.pmid: 18820478
references.citation: Eur J Cell Biol. 2009 Apr;88(4):203-14
references.pmid: 19019491
references.citation: J Cell Biol. 2009 Jan 12;184(1):31-44
references.pmid: 19124654
references.citation: FEBS Lett. 2006 Feb 20;580(5):1263-8
references.pmid: 16445915
references.citation: Methods. 1999 Nov;19(3):362-72
references.pmid: 10579931
references.citation: Science. 2007 Nov 30;318(5855):1408-12
references.pmid: 18048680
references.citation: Dev Cell. 2007 Jun;12(6):863-72
references.pmid: 17543860
references.citation: Trends Cell Biol. 1998 Dec;8(12):467-70
references.pmid: 9861667
references.citation: Nat Rev Mol Cell Biol. 2002 Nov;3(11):848-58
references.pmid: 12415302
references.citation: Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10428-33
references.pmid: 15232008
references.citation: Development. 2007 Mar;134(5):901-8
references.pmid: 17267447
references.citation: J Struct Biol. 1998;122(1-2):42-66
references.pmid: 9724605
references.citation: Cell. 2008 Jun 27;133(7):1175-87
references.pmid: 18585352
references.citation: Mol Biol Cell. 2004 Feb;15(2):600-10
references.pmid: 14617811
references.citation: Development. 2001 Dec;128(24):5039-50
references.pmid: 11748140
references.citation: Hum Mol Genet. 2007 Dec 1;16(23):2816-33
references.pmid: 17761684
references.citation: Dev Cell. 2007 Jun;12(6):873-85
references.pmid: 17543861
references.citation: Proc Natl Acad Sci U S A. 2009 Feb 17;106(7):2194-9
references.pmid: 19164528
references.citation: Hum Mol Genet. 2009 Sep 15;18(18):3462-9
references.pmid: 19542096
references.citation: Dev Biol. 1999 Jul 1;211(1):109-23
references.pmid: 10373309
references.citation: Nat Rev Mol Cell Biol. 2004 Jul;5(7):542-53
references.pmid: 15232572
references.citation: Genetics. 2004 Nov;168(3):1385-93
references.pmid: 15579692