title: Various Themes of Myosin Regulation.
abstract: Members of the myosin superfamily are actin-based molecular motors that are indispensable for cellular homeostasis. The vast functional and structural diversity of myosins accounts for the variety and complexity of the underlying allosteric regulatory mechanisms that determine the activation or inhibition of myosin motor activity and enable precise timing and spatial aspects of myosin function at the cellular level. This review focuses on the molecular basis of posttranslational regulation of eukaryotic myosins from different classes across species by allosteric intrinsic and extrinsic effectors. First, we highlight the impact of heavy and light chain phosphorylation. Second, we outline intramolecular regulatory mechanisms such as autoinhibition and subsequent activation. Third, we discuss diverse extramolecular allosteric mechanisms ranging from actin-linked regulatory mechanisms to myosin:cargo interactions. At last, we briefly outline the allosteric regulation of myosins with synthetic compounds.
authors.affiliation: Laboratory of Molecular Physiology, National Heart, Lung and Blood Institute, National Institutes of Health, 50 South Drive, B50/3529, Bethesda, MD 20892-8015, USA. Electronic address: sarah.heissler@nih.gov.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Heissler
authors.affiliation: Laboratory of Molecular Physiology, National Heart, Lung and Blood Institute, National Institutes of Health, 50 South Drive, B50/3529, Bethesda, MD 20892-8015, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Sellers
mesh_terms: D000494:Allosteric Regulation; D020409:Molecular Motor Proteins / Q000737:chemistry* / Q000378:metabolism*; D009218:Myosins / Q000737:chemistry* / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational
chemical_list: D020409:Molecular Motor Proteins; D009218:Myosins
keywords: actin; cytoskeleton; inhibitor; posttranslational regulation
references.citation: J Biol Chem. 1981 Sep 10;256(17):9274-8
references.pmid: 6114959
references.citation: J Biol Chem. 1981 Dec 25;256(24):13137-42
references.pmid: 6118372
references.citation: J Biol Chem. 1982 Apr 25;257(8):4529-34
references.pmid: 7200093
references.citation: Proc Natl Acad Sci U S A. 1982 Oct;79(20):6151-5
references.pmid: 6959106
references.citation: Biochemistry. 1982 Dec 21;21(26):6910-5
references.pmid: 6984340
references.citation: Nature. 1983 Mar 31-Apr 6;302(5907):436-9
references.pmid: 6687627
references.citation: J Biol Chem. 1983 Aug 25;258(16):10176-81
references.pmid: 6136503
references.citation: J Biol Chem. 1984 Jul 25;259(14):8808-14
references.pmid: 6235218
references.citation: J Biol Chem. 1985 Dec 15;260(29):15815-9
references.pmid: 2933403
references.citation: J Biol Chem. 1986 Jan 5;261(1):36-9
references.pmid: 3079756
references.citation: J Cell Biol. 1987 May;104(5):1309-23
references.pmid: 3032987
references.citation: J Cell Biol. 1987 Sep;105(3):1319-27
references.pmid: 2958483
references.citation: J Mol Biol. 1988 Sep 5;203(1):173-81
references.pmid: 3054120
references.citation: J Biol Chem. 1989 Jan 25;264(3):1431-6
references.pmid: 2521481
references.citation: J Cell Biol. 1989 Jul;109(1):203-10
references.pmid: 2745547
references.citation: Cancer Res. 2006 May 15;66(10):5173-80
references.pmid: 16707441
references.citation: Mol Biol Cell. 2006 Jul;17(7):2869-81
references.pmid: 16611744
references.citation: Nature. 2006 Jul 13;442(7099):208-11
references.pmid: 16625208
references.citation: J Biol Chem. 2001 Oct 26;276(43):39600-7
references.pmid: 11517222
references.citation: Nature. 2006 Jul 13;442(7099):212-5
references.pmid: 16838021
references.citation: J Biol Chem. 2006 Aug 4;281(31):21789-98
references.pmid: 16757473
references.citation: Cell Motil Cytoskeleton. 2006 Oct;63(10):633-45
references.pmid: 16917816
references.citation: Mol Biol Cell. 2006 Nov;17(11):4856-65
references.pmid: 16971510
references.citation: Nat Cell Biol. 2007 Feb;9(2):176-83
references.pmid: 17187061
references.citation: Biochemistry. 2007 Mar 13;46(10):2779-86
references.pmid: 17298083
references.citation: Biochemistry. 2007 Apr 10;46(14):4280-93
references.pmid: 17367164
references.citation: J Biol Chem. 2007 May 4;282(18):13228-39
references.pmid: 17363376
references.citation: J Biol Chem. 2007 Jul 6;282(27):19534-45
references.pmid: 17488711
references.citation: Mol Biol Cell. 2007 Aug;18(8):3144-55
references.pmid: 17567956
references.citation: J Biol Chem. 2007 Aug 10;282(32):23316-25
references.pmid: 17562702
references.citation: Biochemistry. 2007 Oct 23;46(42):11718-26
references.pmid: 17910470
references.citation: Genome Biol. 2007;8(9):R196
references.pmid: 17877792
references.citation: Proc Natl Acad Sci U S A. 2008 Jan 29;105(4):1140-5
references.pmid: 18216256
references.citation: J Biol Chem. 2008 Feb 22;283(8):4520-7
references.pmid: 18089562
references.citation: Biochemistry. 2008 Feb 26;47(8):2485-96
references.pmid: 18229949
references.citation: J Biochem. 1989 Apr;105(4):638-43
references.pmid: 2527229
references.citation: J Biol Chem. 1989 Nov 15;264(32):19340-8
references.pmid: 2530230
references.citation: J Cell Biol. 1989 Dec;109(6 Pt 1):2887-94
references.pmid: 2531749
references.citation: J Biol Chem. 1990 Feb 5;265(4):2105-10
references.pmid: 2137124
references.citation: J Cell Biol. 1990 Apr;110(4):1137-47
references.pmid: 2139032
references.citation: Biochemistry. 1991 Jan 29;30(4):966-70
references.pmid: 1899200
references.citation: RNA. 2008 Mar;14(3):491-502
references.pmid: 18218704
references.citation: Proc Natl Acad Sci U S A. 2008 Apr 15;105(15):5710-5
references.pmid: 18391215
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9616-20
references.pmid: 18599451
references.citation: PLoS Genet. 2008;4(10):e1000207
references.pmid: 18833301
references.citation: Cell. 2008 Oct 31;135(3):535-48
references.pmid: 18984164
references.citation: J Biol Chem. 2008 Nov 14;283(46):32014-23
references.pmid: 18772133
references.citation: J Cell Biol. 1999 Nov 29;147(5):1039-48
references.pmid: 10579723
references.citation: J Cell Biol. 1999 Dec 27;147(7):1385-90
references.pmid: 10613897
references.citation: Biochim Biophys Acta. 2000 Mar 17;1496(1):3-22
references.pmid: 10722873
references.citation: Physiol Rev. 2000 Apr;80(2):853-924
references.pmid: 10747208
references.citation: Biochemistry. 2000 May 9;39(18):5555-60
references.pmid: 10820029
references.citation: Biochemistry. 2000 Sep 19;39(37):11441-51
references.pmid: 10985790
references.citation: J Biol Chem. 2000 Dec 29;275(52):41273-7
references.pmid: 11018047
references.citation: J Cell Sci. 2001 Mar;114(Pt 6):1091-100
references.pmid: 11228153
references.citation: Biochemistry. 2001 Mar 27;40(12):3606-14
references.pmid: 11297427
references.citation: News Physiol Sci. 2001 Apr;16:49-55
references.pmid: 11390948
references.citation: Curr Biol. 2001 Jul 24;11(14):1131-5
references.pmid: 11509238
references.citation: Science. 2001 Aug 17;293(5533):1317-20
references.pmid: 11509731
references.citation: J Biol Chem. 2001 Aug 24;276(34):32373-81
references.pmid: 11423557
references.citation: Nat Cell Biol. 2002 Jan;4(1):83-8
references.pmid: 11744924
references.citation: EMBO J. 2002 Jun 3;21(11):2517-25
references.pmid: 12032065
references.citation: J Biol Chem. 2002 Jul 12;277(28):25423-30
references.pmid: 11980908
references.citation: Nat Cell Biol. 2002 Jul;4(7):469-77
references.pmid: 12055636
references.citation: Biochemistry. 2002 Oct 15;41(41):12450-6
references.pmid: 12369835
references.citation: J Biol Chem. 2002 Nov 8;277(45):43096-103
references.pmid: 12221080
references.citation: J Muscle Res Cell Motil. 2002;23(4):305-8
references.pmid: 12630704
references.citation: Mol Biol Cell. 2003 Mar;14(3):1002-16
references.pmid: 12631719
references.citation: Science. 2003 Mar 14;299(5613):1743-7
references.pmid: 12637748
references.citation: Nat Rev Mol Cell Biol. 2003 Jul;4(7):517-29
references.pmid: 12838335
references.citation: J Biol Chem. 2003 Jul 25;278(30):27439-48
references.pmid: 12704189
references.citation: Biochem J. 2003 Sep 15;374(Pt 3):697-705
references.pmid: 12826013
references.citation: J Biol Chem. 2004 Jan 23;279(4):2333-6
references.pmid: 14634000
references.citation: Biochem Biophys Res Commun. 2004 Mar 12;315(3):538-45
references.pmid: 14975734
references.citation: FEBS Lett. 1977 Sep 15;81(2):386-90
references.pmid: 200479
references.citation: FEBS Lett. 1978 Apr 15;88(2):322-6
references.pmid: 206468
references.citation: Proc Natl Acad Sci U S A. 1979 Jun;76(6):2620-4
references.pmid: 156922
references.citation: Nature. 1980 Sep 18;287(5779):233-5
references.pmid: 6893621
references.citation: Proc Natl Acad Sci U S A. 1980 Dec;77(12):7292-6
references.pmid: 6452632
references.citation: J Cell Biol. 2004 Mar 15;164(6):877-86
references.pmid: 15007063
references.citation: Nat Cell Biol. 2004 Jun;6(6):523-31
references.pmid: 15156152
references.citation: Biochem Biophys Res Commun. 2004 Jul 30;320(3):1020-5
references.pmid: 15240150
references.citation: J Biol Chem. 2004 Aug 20;279(34):35557-63
references.pmid: 15205456
references.citation: Proteins. 2004 Nov 15;57(3):433-43
references.pmid: 15382234
references.citation: Cell. 2012 Jul 20;150(2):327-38
references.pmid: 22817895
references.citation: Curr Biol. 2012 Aug 7;22(15):1410-6
references.pmid: 22704989
references.citation: FEBS Lett. 2012 Sep 21;586(19):3208-14
references.pmid: 22884421
references.citation: Curr Biol. 2012 Sep 25;22(18):1688-92
references.pmid: 22863317
references.citation: J Biol Chem. 2012 Oct 12;287(42):35021-35
references.pmid: 22936804
references.citation: Dev Cell. 2012 Oct 16;23(4):769-81
references.pmid: 23079598
references.citation: Cell Mol Life Sci. 2013 Jan;70(1):1-21
references.pmid: 22565821
references.citation: Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):E23-32
references.pmid: 23248278
references.citation: Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):E33-40
references.pmid: 23248285
references.citation: Nat Neurosci. 2013 Mar;16(3):365-74
references.pmid: 23334578
references.citation: J Biol Chem. 2013 Mar 29;288(13):9532-48
references.pmid: 23382379
references.citation: Cell. 2013 Apr 11;153(2):293-305
references.pmid: 23582321
references.citation: J Biol Chem. 2013 May 10;288(19):13446-54
references.pmid: 23530050
references.citation: Proc Natl Acad Sci U S A. 2013 May 21;110(21):8561-6
references.pmid: 23650385
references.citation: J Biol Chem. 2013 Nov 15;288(46):33398-410
references.pmid: 24072716
references.citation: Biochemistry. 2013 Oct 29;52(43):7641-7
references.pmid: 24083890
references.citation: Biochemistry. 2014 Jan 21;53(2):350-60
references.pmid: 24393048
references.citation: Elife. 2014;3:e01603
references.pmid: 24520162
references.citation: Dev Cell. 2014 Mar 10;28(5):520-33
references.pmid: 24636257
references.citation: Curr Biol. 2014 May 19;24(10):1160-6
references.pmid: 24814144
references.citation: Nat Struct Mol Biol. 2013 Aug;20(8):952-7
references.pmid: 23812374
references.citation: PLoS One. 2013;8(7):e70636
references.pmid: 23923011
references.citation: J Biol Chem. 2013 Sep 13;288(37):26709-20
references.pmid: 23897814
references.citation: PLoS One. 2013;8(9):e74936
references.pmid: 24069366
references.citation: J Biol Chem. 2013 Oct 11;288(41):29313-22
references.pmid: 23979131
references.citation: Mol Biol Cell. 2013 Nov;24(21):3420-34
references.pmid: 24006491
references.citation: J Biol Chem. 1991 Jul 5;266(19):12115-8
references.pmid: 2061300
references.citation: J Cell Biol. 1993 Aug;122(3):613-21
references.pmid: 8335688
references.citation: Cell. 1993 Oct 22;75(2):363-71
references.pmid: 7691416
references.citation: Nature. 1994 Mar 24;368(6469):306-12
references.pmid: 8127365
references.citation: Cell Motil Cytoskeleton. 1994;27(1):41-8
references.pmid: 8194109
references.citation: J Cell Biol. 1994 Jul;126(2):375-89
references.pmid: 8034741
references.citation: J Cell Biol. 1994 Dec;127(6 Pt 2):1945-55
references.pmid: 7806572
references.citation: Cell Motil Cytoskeleton. 1994;29(1):29-45
references.pmid: 7820856
references.citation: J Biol Chem. 1995 Feb 3;270(5):2171-5
references.pmid: 7836446
references.citation: Biophys J. 1995 Apr;68(4 Suppl):224S
references.pmid: 7787078
references.citation: Cell Motil Cytoskeleton. 1995;31(2):87-92
references.pmid: 7553910
references.citation: Structure. 1996 Jan 15;4(1):21-32
references.pmid: 8805510
references.citation: Biophys J. 1996 Aug;71(2):898-907
references.pmid: 8842229
references.citation: Structure. 1996 Dec 15;4(12):1475-90
references.pmid: 8994973
references.citation: Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1092-5
references.pmid: 9037011
references.citation: Biochemistry. 1997 Dec 23;36(51):16321-7
references.pmid: 9405067
references.citation: Mol Biol Cell. 1998 Jan;9(1):75-88
references.pmid: 9436992
references.citation: Biochemistry. 1998 Feb 17;37(7):1989-2003
references.pmid: 9485326
references.citation: J Biol Chem. 1998 Aug 7;273(32):20481-6
references.pmid: 9685403
references.citation: J Cell Biol. 1998 Dec 14;143(6):1535-45
references.pmid: 9852149
references.citation: J Biol Chem. 1999 Jul 30;274(31):21575-80
references.pmid: 10419463
references.citation: Biochemistry. 2004 Nov 23;43(46):14832-9
references.pmid: 15544354
references.citation: J Muscle Res Cell Motil. 2004;25(4-5):337-41
references.pmid: 15548862
references.citation: Biochemistry. 2005 Jan 18;44(2):584-8
references.pmid: 15641783
references.citation: Nat Struct Mol Biol. 2005 Feb;12(2):127-32
references.pmid: 15665867
references.citation: J Biol Chem. 2005 Feb 18;280(7):6072-9
references.pmid: 15579901
references.citation: J Biol Chem. 2005 Feb 18;280(7):6064-71
references.pmid: 15579903
references.citation: Annu Rev Physiol. 2005;67:39-67
references.pmid: 15709952
references.citation: Nat Struct Mol Biol. 2005 Apr;12(4):378-9
references.pmid: 15750603
references.citation: Biochemistry. 2005 May 10;44(18):6867-76
references.pmid: 15865432
references.citation: J Biol Chem. 2005 May 6;280(18):17815-22
references.pmid: 15760894
references.citation: Trends Cell Biol. 2005 Jun;15(6):333-41
references.pmid: 15953552
references.citation: Physiology (Bethesda). 2005 Aug;20:239-51
references.pmid: 16024512
references.citation: BMC Cell Biol. 2011;12:52
references.pmid: 22136066
references.citation: Curr Biol. 2012 Feb 21;22(4):320-5
references.pmid: 22264607
references.citation: Proc Natl Acad Sci U S A. 2012 Apr 17;109(16):6048-53
references.pmid: 22460785
references.citation: J Cell Sci. 2012 Apr 1;125(Pt 7):1627-32
references.pmid: 22566666
references.citation: Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9402-7
references.pmid: 22647605
references.citation: J Muscle Res Cell Motil. 2005;26(4-5):183-9
references.pmid: 16179973
references.citation: J Biol Chem. 2005 Dec 16;280(50):41562-7
references.pmid: 16254000
references.citation: J Cell Sci. 2006 Feb 1;119(Pt 3):550-8
references.pmid: 16443752
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3118-23
references.pmid: 16492791
references.citation: Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5746-51
references.pmid: 16585515
references.citation: Bioarchitecture. 2013 Jul-Aug;3(4):77-85
references.pmid: 24002531
references.citation: Biochemistry. 2014 Jun 24;53(24):4015-24
references.pmid: 24873380
references.citation: Angew Chem Int Ed Engl. 2014 Jul 28;53(31):8211-5
references.pmid: 24954740
references.citation: Curr Biol. 2014 Sep 8;24(17):1958-68
references.pmid: 25131674
references.citation: Acc Chem Res. 2014 Oct 21;47(10):3061-70
references.pmid: 25230296
references.citation: Dev Cell. 2014 Dec 22;31(6):747-60
references.pmid: 25482883
references.citation: Curr Biol. 2015 Jan 19;25(2):175-86
references.pmid: 25544611
references.citation: Elife. 2015;4. doi: 10.7554/eLife.05472
references.pmid: 25738229
references.citation: Curr Biol. 2015 Mar 30;25(7):942-8
references.pmid: 25754640
references.citation: FASEB J. 2015 Apr;29(4):1456-66
references.pmid: 25636739
references.citation: Exp Cell Res. 2015 May 15;334(1):2-9
references.pmid: 25655283
references.citation: Arch Biochem Biophys. 2015 Aug 15;580:14-21
references.pmid: 26116789
references.citation: Curr Biol. 2015 Aug 3;25(15):2057-62
references.pmid: 26190073
references.citation: Nat Commun. 2015;6:7974
references.pmid: 26246073
references.citation: Bioarchitecture. 2014;4(6):169-88
references.pmid: 26155737
references.citation: J Mol Biol. 2008 Dec 26;384(4):780-97
references.pmid: 18951904
references.citation: Nat Struct Mol Biol. 2009 Jan;16(1):80-8
references.pmid: 19122661
references.citation: J Mol Biol. 2009 Jan 16;385(2):423-31
references.pmid: 18976661
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4189-94
references.pmid: 19255446
references.citation: Nat Cell Biol. 2009 Apr;11(4):443-50
references.pmid: 19287378
references.citation: Proc Natl Acad Sci U S A. 2009 May 26;106(21):8483-8
references.pmid: 19423668
references.citation: Annu Rev Biochem. 2009;78:797-825
references.pmid: 19489734
references.citation: Curr Biol. 2009 Jun 9;19(11):967-73
references.pmid: 19398338
references.citation: Proc Natl Acad Sci U S A. 2009 Jun 16;106(24):9685-90
references.pmid: 19478066
references.citation: Proc Natl Acad Sci U S A. 2009 Jul 21;106(29):11972-7
references.pmid: 19574460
references.citation: Cell. 2009 Aug 7;138(3):537-48
references.pmid: 19665975
references.citation: Mol Cell. 2009 Aug 14;35(3):305-15
references.pmid: 19664948
references.citation: Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17320-4
references.pmid: 19805065
references.citation: Heart Fail Rev. 2009 Dec;14(4):289-98
references.pmid: 19234787
references.citation: J Cell Sci. 2009 Nov 1;122(Pt 21):3856-61
references.pmid: 19808887
references.citation: Nat Struct Mol Biol. 2010 Apr;17(4):485-91
references.pmid: 20364131
references.citation: Proc Natl Acad Sci U S A. 2010 Apr 13;107(15):6799-804
references.pmid: 20351242
references.citation: Trends Cell Biol. 2010 Jul;20(7):418-26
references.pmid: 20471271
references.citation: J Biol Chem. 2010 Aug 20;285(34):26608-17
references.pmid: 20538587
references.citation: Curr Biol. 2010 Aug 24;20(16):1423-31
references.pmid: 20705471
references.citation: J Cell Sci. 2010 Oct 15;123(Pt 20):3525-34
references.pmid: 20930142
references.citation: Angew Chem Int Ed Engl. 2010 Nov 2;49(45):8484-8
references.pmid: 20878825
references.citation: J Biol Chem. 2010 Nov 12;285(46):35770-82
references.pmid: 20826793
references.citation: J Mol Biol. 2011 Jan 7;405(1):105-12
references.pmid: 20970430
references.citation: Nat Cell Biol. 2011 Jan;13(1):40-8
references.pmid: 21151132
references.citation: Biophys J. 2011 Jan 19;100(2):430-9
references.pmid: 21244839
references.citation: Proc Natl Acad Sci U S A. 2011 Jan 25;108(4):1421-6
references.pmid: 21205888
references.citation: Science. 2011 Mar 18;331(6023):1439-43
references.pmid: 21415352
references.citation: J Biol Chem. 2011 Mar 25;286(12):9941-7
references.pmid: 21257758
references.citation: Biochim Biophys Acta. 2011 May;1813(5):913-21
references.pmid: 21262274
references.citation: J Mol Biol. 2011 May 20;408(5):863-78
references.pmid: 21419133
references.citation: Proc Natl Acad Sci U S A. 2011 Apr 26;108(17):7028-33
references.pmid: 21482763
references.citation: J Biol Chem. 2011 Jun 17;286(24):21191-202
references.pmid: 21478157
references.citation: Nat Struct Mol Biol. 2011 Jul;18(7):783-8
references.pmid: 21666676
references.citation: J Biol Chem. 2011 Aug 26;286(34):29700-8
references.pmid: 21680745
references.citation: J Neurochem. 2011 Nov;119(4):772-84
references.pmid: 21895655
references.citation: Semin Cell Dev Biol. 2011 Dec;22(9):961-7
references.pmid: 22001381
references.citation: Nat Rev Mol Cell Biol. 2012 Jan;13(1):13-26
references.pmid: 22146746
references.citation: Cell Mol Life Sci. 2012 Jan;69(2):299-311
references.pmid: 21687988