title: LIS1 and NudE induce a persistent dynein force-producing state.
abstract: Cytoplasmic dynein is responsible for many aspects of cellular and subcellular movement. LIS1, NudE, and NudEL are dynein interactors initially implicated in brain developmental disease but now known to be required in cell migration, nuclear, centrosomal, and microtubule transport, mitosis, and growth cone motility. Identification of a specific role for these proteins in cytoplasmic dynein motor regulation has remained elusive. We find that NudE stably recruits LIS1 to the dynein holoenzyme molecule, where LIS1 interacts with the motor domain during the prepowerstroke state of the dynein crossbridge cycle. NudE abrogates dynein force production, whereas LIS1 alone or with NudE induces a persistent-force dynein state that improves ensemble function of multiple dyneins for transport under high-load conditions. These results likely explain the requirement for LIS1 and NudE in the transport of nuclei, centrosomes, chromosomes, and the microtubule cytoskeleton as well as the particular sensitivity of migrating neurons to reduced LIS1 expression.
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: McKenney
authors.forename: Michael
authors.initials: M
authors.lastname: Vershinin
authors.forename: Ambarish
authors.initials: A
authors.lastname: Kunwar
authors.forename: Richard B
authors.initials: RB
authors.lastname: Vallee
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gross
mesh_terms: D000465:Algorithms; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D002522:Chlorocebus aethiops; D004398:Dyneins / Q000378:metabolism*; D006801:Humans; D016547:Kinesins / Q000378:metabolism; D054082:Lissencephaly / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D004398:Dyneins; D016547:Kinesins
references.citation: Nat Cell Biol. 2000 Jan;2(1):20-4
references.pmid: 10620802
references.citation: Nature. 1993 Aug 19;364(6439):717-21
references.pmid: 8355785
references.citation: Curr Biol. 2001 May 1;11(9):719-24
references.pmid: 11369237
references.citation: J Cell Biol. 2003 Dec 22;163(6):1205-11
references.pmid: 14691133
references.citation: J Cell Biol. 1987 Sep;105(3):1273-82
references.pmid: 2958482
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):8938-43
references.pmid: 18579780
references.citation: Mol Biol Cell. 2006 Feb;17(2):680-9
references.pmid: 16291865
references.citation: Mol Biol Cell. 2007 Jul;18(7):2656-66
references.pmid: 17494871
references.citation: EMBO J. 2008 Oct 8;27(19):2471-83
references.pmid: 18784752
references.citation: Cell Host Microbe. 2009 Dec 17;6(6):523-35
references.pmid: 20006841
references.citation: PLoS Biol. 2009 Apr 21;7(4):e1000087
references.pmid: 19385717
references.citation: Neuron. 2004 Dec 2;44(5):809-21
references.pmid: 15572112
references.citation: Nature. 1987 Nov 12-18;330(6144):181-3
references.pmid: 3670402
references.citation: Nat Cell Biol. 2000 Nov;2(11):784-91
references.pmid: 11056532
references.citation: Cell. 2008 Dec 12;135(6):1098-107
references.pmid: 19070579
references.citation: Neuron. 2000 Dec;28(3):665-79
references.pmid: 11163258
references.citation: Nat Genet. 1998 Aug;19(4):333-9
references.pmid: 9697693
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 17;106(46):19381-6
references.pmid: 19864630
references.citation: Nature. 1980 Sep 18;287(5779):233-5
references.pmid: 6893621
references.citation: Nat Cell Biol. 2006 Jun;8(6):562-70
references.pmid: 16715075
references.citation: Biochemistry. 2004 Sep 7;43(35):11266-74
references.pmid: 15366936
references.citation: Structure. 2007 Nov;15(11):1467-81
references.pmid: 17997972
references.citation: Mol Biol Cell. 1995 Mar;6(3):297-310
references.pmid: 7612965
references.citation: Neuron. 2000 Dec;28(3):697-711
references.pmid: 11163260
references.citation: J Cell Biol. 2005 Sep 12;170(6):935-45
references.pmid: 16144905
references.citation: Birth Defects Orig Artic Ser. 1987;23(1):225-41
references.pmid: 3472611
references.citation: J Cell Biol. 2004 Feb 16;164(4):557-66
references.pmid: 14970193
references.citation: J Biol Chem. 2004 Jan 23;279(4):2333-6
references.pmid: 14634000
references.citation: Dev Cell. 2008 Mar;14(3):342-53
references.pmid: 18331715
references.citation: J Neurosci. 2006 Feb 15;26(7):2132-9
references.pmid: 16481446
references.citation: Nature. 1987 Dec 17-23;330(6149):672-4
references.pmid: 2960903
references.citation: J Biol Chem. 1999 May 21;274(21):14617-23
references.pmid: 10329654
references.citation: Nat Struct Mol Biol. 2009 Mar;16(3):325-33
references.pmid: 19198589
references.citation: J Cell Biol. 2000 Aug 7;150(3):681-8
references.pmid: 10931877
references.citation: J Cell Biol. 2007 Aug 13;178(4):583-94
references.pmid: 17682047
references.citation: Mol Cell Biol. 2003 Feb;23(4):1239-50
references.pmid: 12556484
references.citation: Cell. 2007 Nov 30;131(5):952-65
references.pmid: 18045537
references.citation: Curr Biol. 2010 Apr 27;20(8):687-96
references.pmid: 20399098
references.citation: J Biol Chem. 2005 Sep 23;280(38):33045-54
references.pmid: 16030013
references.citation: Curr Biol. 2008 Aug 26;18(16):1173-83
references.pmid: 18701289
references.citation: Annu Rev Biophys Biomol Struct. 2001;30:105-28
references.pmid: 11340054
references.citation: J Cell Biol. 2004 Mar 15;164(6):877-86
references.pmid: 15007063
references.citation: Mol Cell Biol. 2002 May;22(9):3089-102
references.pmid: 11940666
references.citation: Nature. 2004 Feb 12;427(6975):649-52
references.pmid: 14961123
references.citation: Neuron. 2004 Oct 14;44(2):263-77
references.pmid: 15473966
references.citation: Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8680-5
references.pmid: 16731631
references.citation: J Cell Biol. 2002 Mar 18;156(6):959-68
references.pmid: 11889140
references.citation: Nat Neurosci. 2007 Aug;10(8):970-9
references.pmid: 17618279
references.citation: Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5741-5
references.pmid: 16585530
references.citation: Neuron. 2000 Dec;28(3):681-96
references.pmid: 11163259
references.citation: Curr Biol. 2005 Dec 6;15(23):2075-85
references.pmid: 16332532
references.citation: Mol Biol Cell. 2005 Nov;16(11):5127-40
references.pmid: 16107559
references.citation: Curr Biol. 2007 Jul 3;17(13):1173-9
references.pmid: 17600710
references.citation: Nat Cell Biol. 2000 Nov;2(11):767-75
references.pmid: 11056530
references.citation: EMBO J. 1997 Dec 1;16(23):6977-84
references.pmid: 9384577
references.citation: Nat Cell Biol. 2005 Sep;7(9):861-9
references.pmid: 16100513
references.citation: Cell. 2006 Jul 28;126(2):335-48
references.pmid: 16873064
references.citation: Structure. 2007 Apr;15(4):429-40
references.pmid: 17437715
references.citation: Traffic. 2008 Jun;9(6):882-92
references.pmid: 18373727
references.citation: J Biol Chem. 1983 Nov 25;258(22):13841-6
references.pmid: 6227618
references.citation: Nature. 2003 Feb 13;421(6924):715-8
references.pmid: 12610617
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16134-9
references.pmid: 17911268
references.citation: J Neurosci. 2007 May 23;27(21):5823-34
references.pmid: 17522326
references.citation: Cell. 1994 Jun 3;77(5):773-84
references.pmid: 8205624