title: Lamins at the crossroads of mechanosignaling.
abstract: The intermediate filament proteins, A- and B-type lamins, form the nuclear lamina scaffold adjacent to the inner nuclear membrane. B-type lamins confer elasticity, while A-type lamins lend viscosity and stiffness to nuclei. Lamins also contribute to chromatin regulation and various signaling pathways affecting gene expression. The mechanical roles of lamins and their functions in gene regulation are often viewed as independent activities, but recent findings suggest a highly cross-linked and interdependent regulation of these different functions, particularly in mechanosignaling. In this newly emerging concept, lamins act as a "mechanostat" that senses forces from outside and responds to tension by reinforcing the cytoskeleton and the extracellular matrix. A-type lamins, emerin, and the linker of the nucleoskeleton and cytoskeleton (LINC) complex directly transmit forces from the extracellular matrix into the nucleus. These mechanical forces lead to changes in the molecular structure, modification, and assembly state of A-type lamins. This in turn activates a tension-induced "inside-out signaling" through which the nucleus feeds back to the cytoskeleton and the extracellular matrix to balance outside and inside forces. These functions regulate differentiation and may be impaired in lamin-linked diseases, leading to cellular phenotypes, particularly in mechanical load-bearing tissues.
authors: Max F. Perutz Laboratories, Department of Medical Biochemistry, Medical University Vienna, A-1030 Vienna, Austria.
authors: Selma
authors: S
authors: Osmanagic-Myers
authors: Max F. Perutz Laboratories, Department of Medical Biochemistry, Medical University Vienna, A-1030 Vienna, Austria.
authors: Thomas
authors: T
authors: Dechat
authors: Max F. Perutz Laboratories, Department of Medical Biochemistry, Medical University Vienna, A-1030 Vienna, Austria roland.foisner@meduniwien.ac.at.
authors: Roland
authors: R
authors: Foisner
mesh_terms: D000818:Animals; D002465:Cell Movement; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D034882:Lamins / Q000737:chemistry / Q000378:metabolism*; D040542:Mechanotransduction, Cellular; D009154:Mutation
chemical_list: D034882:Lamins
keywords: LINC complex; cytoskeleton; extracellular matrix; lamins; mechanosensing; mechanotransduction
references: Bioessays. 2014 Jan;36(1):75-83
references: 24272858
references: J Cell Sci. 2010 Nov 15;123(Pt 22):3893-900
references: 20980393
references: Cell. 2013 Jan 17;152(1-2):97-108
references: 23332748
references: Biochem Biophys Res Commun. 2013 Oct 11;440(1):8-13
references: 23998933
references: Biophys J. 2007 Oct 1;93(7):2542-52
references: 17631533
references: J Biol Chem. 2002 May 17;277(20):17381-4
references: 11901143
references: Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4598-603
references: 12684533
references: J Cell Mol Med. 2009 Jun;13(6):1059-85
references: 19210577
references: Hum Mol Genet. 2004 Nov 1;13(21):2567-80
references: 15367494
references: J Cell Sci. 2009 Feb 1;122(Pt 3):401-13
references: 19126678
references: Curr Biol. 2011 Oct 11;21(19):1603-14
references: 21962710
references: J Cell Sci. 2014 Jul 1;127(Pt 13):2873-84
references: 24806962
references: Nucleus. 2012 Nov-Dec;3(6):552-64
references: 22990521
references: Cold Spring Harb Symp Quant Biol. 2010;75:555-65
references: 21467137
references: Science. 2013 Aug 30;341(6149):1240104
references: 23990565
references: J Mol Biol. 2009 Mar 13;386(5):1392-402
references: 19109977
references: Mol Biol Cell. 2014 Apr;25(8):1287-97
references: 24523288
references: Exp Cell Res. 2006 Feb 15;312(4):423-33
references: 16337188
references: J Cell Biol. 2007 Jan 15;176(2):163-72
references: 17227891
references: Biol Cell. 2009 Sep;101(9):541-54
references: 19323649
references: J Pathol. 2012 Jan;226(2):316-25
references: 21953297
references: Mol Biol Cell. 2002 Dec;13(12):4401-13
references: 12475961
references: Nature. 2013 May 23;497(7450):507-11
references: 23644458
references: Mol Biol Cell. 2011 Dec;22(23):4683-93
references: 21976703
references: Exp Cell Res. 2007 May 15;313(9):1897-910
references: 17448463
references: Nature. 1986 Oct 9-15;323(6088):560-4
references: 3762708
references: Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):4955-60
references: 17360326
references: J Cell Biol. 2009 Dec 28;187(7):945-57
references: 20038676
references: J Cell Biol. 2000 Sep 18;150(6):1251-62
references: 10995432
references: Am J Clin Pathol. 1970 Feb;53(2):243-53
references: 5415913
references: J Am Coll Cardiol. 2009 May 12;53(19):1752-9
references: 19422981
references: J Cell Sci. 2001 Jul;114(Pt 14):2577-90
references: 11683386
references: Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):5076-81
references: 20145110
references: Cell. 2003 May 2;113(3):329-42
references: 12732141
references: Nucleus. 2014 Jan-Feb;5(1):66-74
references: 24637396
references: Sci Rep. 2013;3:1087
references: 23336069
references: J Struct Biol. 1996 Jul-Aug;117(1):1-15
references: 8776884
references: Cell. 1990 May 18;61(4):579-89
references: 2344612
references: Cold Spring Harb Perspect Biol. 2010 Nov;2(11):a000547
references: 20826548
references: Cell. 2012 Apr 27;149(3):509-10
references: 22541423
references: J Biol Chem. 2006 Sep 1;281(35):25768-80
references: 16825190
references: Mol Cell. 2010 May 28;38(4):603-13
references: 20513434
references: Nat Commun. 2014;5:4525
references: 25077739
references: Cell. 1980 Jan;19(1):277-87
references: 7357605
references: Nat Cell Biol. 2008 Nov;10(11):1341-8
references: 18849980
references: Mol Cell Biol. 2014 Dec;34(24):4534-44
references: 25312645
references: Cell Cycle. 2009 May 15;8(10):1488-93
references: 19377295
references: Dev Cell. 2010 Sep 14;19(3):413-25
references: 20833363
references: Cell Res. 2013 Dec;23(12):1420-3
references: 23979018
references: J Struct Biol. 2012 Jan;177(1):106-12
references: 22079399
references: J Clin Invest. 2004 Feb;113(3):370-8
references: 14755334
references: Adv Exp Med Biol. 2014;773:127-42
references: 24563346
references: Cell. 2012 Apr 27;149(3):565-77
references: 22541428
references: Eur J Cell Biol. 1991 Aug;55(2):191-9
references: 1935984
references: J Cell Biol. 2012 Sep 17;198(6):981-90
references: 22986494
references: Nature. 2005 Sep 15;437(7057):426-31
references: 16163360
references: J Biol Chem. 1997 Nov 21;272(47):29693-7
references: 9368037
references: Biophys J. 2010 Jul 7;99(1):115-23
references: 20655839
references: J Cell Biol. 1993 Mar;120(6):1293-304
references: 8449977
references: Science. 2011 Dec 23;334(6063):1706-10
references: 22116031
references: J Cell Biol. 2005 Aug 29;170(5):781-91
references: 16115958
references: Curr Top Dev Biol. 2014;109:1-52
references: 24947235
references: Integr Biol (Camb). 2013 Mar;5(3):569-77
references: 23370891
references: Nucleus. 2011 Sep-Oct;2(5):425-33
references: 22033280
references: Exp Cell Res. 2007 Jun 10;313(10):2157-66
references: 17451683
references: Nature. 2008 Jun 12;453(7197):948-51
references: 18463634
references: Histochem Cell Biol. 2013 Jul;140(1):3-12
references: 23744527
references: Biophys J. 2006 Dec 15;91(12):4649-64
references: 16997877
references: Circ Res. 2006 Oct 13;99(8):837-44
references: 16990566
references: Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10428-33
references: 15232008
references: Hum Mol Genet. 2013 Jun 15;22(12):2335-49
references: 23427149
references: Nat Clin Pract Cardiovasc Med. 2009 Jan;6(1):16-26
references: 19029993
references: J Cell Biol. 2006 Jan 2;172(1):41-53
references: 16380439
references: Biochemistry. 2014 Nov 25;53(46):7247-58
references: 25343322
references: Genes Dev. 2010 Apr 15;24(8):766-82
references: 20395364
references: Hum Mol Genet. 2013 Jul 15;22(14):2852-69
references: 23535822
references: Curr Opin Cell Biol. 2013 Feb;25(1):57-62
references: 23149102
references: Acta Myol. 2013 May;32(1):7-17
references: 23853504
references: Biophys J. 2013 May 21;104(10):2246-53
references: 23708364
references: EMBO Rep. 2007 Oct;8(10):914-9
references: 17906672
references: Mol Biol Cell. 2008 Dec;19(12):5398-408
references: 18923140
references: J Cell Biol. 1999 Nov 29;147(5):913-20
references: 10579712
references: Nat Cell Biol. 2008 Apr;10(4):452-9
references: 18311132
references: Science. 2009 Jan 30;323(5914):588-9
references: 19179515
references: J Biol Chem. 2011 Jul 29;286(30):26743-53
references: 21652697
references: Nucleus. 2012 Mar 1;3(2):172-86
references: 22198684
references: Biochemistry. 1999 Apr 6;38(14):4620-32
references: 10194384
references: J Cell Sci. 2014 Apr 15;127(Pt 8):1792-804
references: 24522183
references: Biophys J. 2012 Dec 19;103(12):2423-31
references: 23260044
references: Nucleus. 2013 Jan-Feb;4(1):53-60
references: 23324457
references: Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):18892-7
references: 24191023
references: Nat Rev Mol Cell Biol. 2009 Jan;10(1):75-82
references: 19197334
references: J Biol Chem. 1990 Jul 25;265(21):12636-41
references: 2373705
references: J Lipid Res. 2005 Dec;46(12):2531-58
references: 16207929
references: J Clin Invest. 2004 Feb;113(3):357-69
references: 14755333
references: Structure. 2002 Jun;10(6):811-23
references: 12057196
references: Genes Dev. 2008 Apr 1;22(7):832-53
references: 18381888
references: Chromosoma. 2013 Mar;122(1-2):13-31
references: 23475188
references: J Biol Chem. 2004 Jan 2;279(1):163-8
references: 14570928
references: J Cell Sci. 2000 Oct;113 Pt 19:3473-84
references: 10984438
references: Genome Res. 2013 Oct;23(10):1580-9
references: 23861385
references: Biophys J. 2008 Apr 1;94(7):2906-13
references: 18178644
references: Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10271-6
references: 16801550
references: J Cell Biol. 2001 Apr 30;153(3):479-89
references: 11331300
references: J Cell Sci. 2012 Mar 1;125(Pt 5):1099-105
references: 22349700
references: Dev Cell. 2013 Mar 11;24(5):447-58
references: 23484852
references: J Biol Chem. 2004 Oct 15;279(42):43462-7
references: 15292200
references: J Struct Biol. 2012 Jan;177(1):113-8
references: 22085746
references: Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):849-54
references: 9023345
references: Adv Exp Med Biol. 2014;773:187-206
references: 24563349
references: Biophys J. 2008 Dec;95(11):5462-75
references: 18790843
references: Phys Rev E Stat Nonlin Soft Matter Phys. 2004 Oct;70(4 Pt 1):041906
references: 15600434
references: Annu Rev Cell Dev Biol. 2014;30:291-315
references: 25062360
references: J Cell Sci. 2008 Jan 15;121(Pt 2):215-25
references: 18187453
references: Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3282-7
references: 19218438
references: J Cell Sci. 2014 Jun 15;127(Pt 12):2683-96
references: 24741066
references: Biochem J. 2005 Apr 1;387(Pt 1):129-38
references: 15479156
references: PLoS Genet. 2014 Sep;10(9):e1004605
references: 25210889
references: Cell. 2012 May 25;149(5):1035-47
references: 22632968
references: Adv Exp Med Biol. 2014;773:415-30
references: 24563359
references: Nat Cell Biol. 2014 Apr;16(4):376-81
references: 24609268
references: Nat Genet. 2002 May;31(1):94-9
references: 11923874
references: J Cell Biol. 2014 Mar 3;204(5):669-82
references: 24567359
references: Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):131-6
references: 21173262
references: J Cell Biol. 2008 Apr 21;181(2):269-80
references: 18426975
references: J Cell Biol. 2010 Nov 29;191(5):967-79
references: 21115804
references: Semin Cell Dev Biol. 2014 May;29:116-24
references: 24374133
references: Aging Cell. 2004 Aug;3(4):235-43
references: 15268757
references: EMBO J. 2006 Jul 26;25(14):3275-85
references: 16858403
references: J Mol Med (Berl). 2012 Dec;90(12):1361-89
references: 23090008
references: Cell. 2013 Jan 31;152(3):584-98
references: 23374351
references: Biochem Biophys Res Commun. 2005 Apr 8;329(2):423-8
references: 15737604
references: J Med Genet. 2005 Mar;42(3):214-20
references: 15744034
references: Curr Biol. 2013 Dec 16;23(24):R1113-21
references: 24355792
references: J Cell Biol. 2008 Nov 17;183(4):653-66
references: 19015316
references: Stem Cells. 2010 Mar 31;28(3):480-8
references: 20039368
references: J Mol Biol. 2003 Jan 10;325(2):241-7
references: 12488092
references: Trends Biochem Sci. 2001 Jan;26(1):41-7
references: 11165516
references: J Cell Biol. 2002 Nov 25;159(4):695-705
references: 12446745
references: EMBO Rep. 2012 Dec;13(12):1070-8
references: 23146893
references: Hum Mol Genet. 2005 Feb 1;14(3):437-45
references: 15601644
references: Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15619-24
references: 17893336
references: Science. 2010 Aug 20;329(5994):956-9
references: 20724637
references: J Biol Chem. 2013 Mar 22;288(12):8610-8
references: 23355469
references: Cold Spring Harb Symp Quant Biol. 2010;75:533-43
references: 21209392
references: Mol Biol Cell. 2013 Dec;24(24):3869-80
references: 24152738
references: J Struct Biol. 1998;122(1-2):42-66
references: 9724605
references: Nucleus. 2011 May-Jun;2(3):195-207
references: 21818413
references: J Cell Sci. 2004 Dec 1;117(Pt 25):6117-28
references: 15546916
references: Arterioscler Thromb Vasc Biol. 2010 Nov;30(11):2301-9
references: 20798379
references: Invest Ophthalmol Vis Sci. 2006 Nov;47(11):4895-904
references: 17065504
references: J Cell Biol. 2006 Apr 10;173(1):83-93
references: 16606692
references: PLoS One. 2012;7(2):e32649
references: 22393432
references: Science. 2008 Jun 6;320(5881):1332-6
references: 18535242
references: Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):180-5
references: 18162544
references: Biochim Biophys Acta. 2007 May;1773(5):675-86
references: 17050008
references: Cell Mol Bioeng. 2009 Sep 1;2(3):341-350
references: 20011623
references: Exp Cell Res. 2010 Aug 15;316(14):2301-12
references: 20580708
references: Nat Commun. 2013;4:2268
references: 23917225
references: Nat Commun. 2012;3:866
references: 22643893
references: J Cell Sci. 2006 Aug 15;119(Pt 16):3265-72
references: 16899817
references: Eur J Cell Biol. 2014 Oct;93(10-12):445-54
references: 25062607
references: Biophys J. 2005 Oct;89(4):2855-64
references: 16055543
references: Genes Dev. 2006 Feb 1;20(3):307-20
references: 16452503
references: Genes Dev. 2008 Dec 15;22(24):3409-21
references: 19141474
references: Prog Biophys Mol Biol. 2014 Aug;115(2-3):76-92
references: 25008017
references: Biochem Biophys Res Commun. 2012 Feb 10;418(2):217-21
references: 22266370
references: Nat Rev Mol Cell Biol. 2014 Dec;15(12):802-12
references: 25355505
references: Nat Rev Mol Cell Biol. 2013 Jan;14(1):13-24
references: 23212477
references: J Cell Sci. 2004 Sep 15;117(Pt 20):4779-86
references: 15331638
references: J Biol Chem. 1993 May 5;268(13):9856-62
references: 8486665
references: Cell. 2013 Mar 14;152(6):1365-75
references: 23498943
references: Curr Biol. 2014 Aug 18;24(16):1909-17
references: 25127216
references: Hum Mol Genet. 2005 Oct 1;14(19):2839-49
references: 16115815
references: Nat Rev Mol Cell Biol. 2011 Nov;12(11):695-708
references: 21971041
references: J Struct Biol. 2006 Aug;155(2):340-50
references: 16713298
references: J Cell Biol. 1991 May;113(3):485-95
references: 2016332
references: J Cell Biol. 2000 Dec 11;151(6):1155-68
references: 11121432
references: J Cell Sci. 1999 Mar;112 ( Pt 6):977-87
references: 10036247
references: PLoS Biol. 2004 Sep;2(9):E231
references: 15328537
references: Nucleus. 2010 Jan-Feb;1(1):40-52
references: 21327104
references: Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):13049-54
references: 12235369
references: EMBO J. 2008 Dec 3;27(23):3198-208
references: 19008859
references: FASEB J. 2011 May;25(5):1474-85
references: 21248241
references: Nature. 2005 Apr 21;434(7036):1040-5
references: 15846350