The Ndc80 loop region facilitates formation of kinetochore attachment to the dynamic microtubule plus end.
Proper chromosome segregation in mitosis relies on correct kinetochore-microtubule (KT-MT) interactions. The KT initially interacts with the lateral surface of a single MT (lateral attachment) extending from a spindle pole and is subsequently anchored at the plus end of the MT (end-on attachment). The conversion from lateral to end-on attachment is crucial because end-on attachment is more robust and thought to be necessary to sustain KT-MT attachment when tension is applied across sister KTs upon their biorientation. The mechanism for this conversion is still elusive. The Ndc80 complex is an essential component of the KT-MT interface, and here we studied a role of the Ndc80 loop region, a distinct motif looping out from the coiled-coil shaft of the complex, in Saccharomyces cerevisiae. With deletions or mutations of the loop region, the lateral KT-MT attachment occurred normally; however, subsequent conversion to end-on attachment was defective, leading to failure in sister KT biorientation. The Ndc80 loop region was required for Ndc80-Dam1 interaction and KT loading of the Dam1 complex, which in turn supported KT tethering to the dynamic MT plus end. The Ndc80 loop region, therefore, has an important role in the conversion from lateral to end-on attachment, a crucial maturation step of KT-MT interaction.
Wellcome Trust Centre for Gene Regulation & Expression, University of Dundee, Dundee DD1 5EH, UK.
Jean-François
JF
Maure
Shinya
S
Komoto
Yusuke
Y
Oku
Akihisa
A
Mino
Sebastiano
S
Pasqualato
Kayo
K
Natsume
Lesley
L
Clayton
Andrea
A
Musacchio
Tomoyuki U
TU
Tanaka
D000595:Amino Acid Sequence; D018386:Kinetochores / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000648:ultrastructure*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D016415:Sequence Alignment
C112472:NDC80 protein, S cerevisiae; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins
Genes Dev. 2007 Dec 15;21(24):3319-30
18079178
Annu Rev Biochem. 2007;76:563-91
17362199
EMBO J. 2009 Sep 2;28(17):2511-31
19629042
Mol Biol Cell. 2003 Aug;14(8):3342-55
12925767
EMBO J. 2001 Feb 15;20(4):777-91
11179222
Nature. 2006 Mar 23;440(7083):565-9
16415853
J Mol Biol. 2008 Nov 21;383(4):894-903
18793650
Cell. 2008 May 2;133(3):427-39
18455984
EMBO J. 2010 Dec 15;29(24):4070-82
21102558
J Cell Biol. 2010 May 17;189(4):713-23
20479468
Nat Rev Mol Cell Biol. 2007 May;8(5):379-93
17426725
Nat Cell Biol. 2000 Aug;2(8):492-9
10934469
Nature. 2005 Nov 17;438(7066):384-8
16292315
J Cell Biol. 2007 Jul 16;178(2):269-81
17620411
Cell. 2000 Mar 17;100(6):619-33
10761928
Curr Biol. 2009 Apr 28;19(8):694-9
19345105
Cell. 2006 Dec 1;127(5):983-97
17129783
Cell. 2009 Mar 6;136(5):865-75
19269365
Curr Opin Cell Biol. 2010 Feb;22(1):57-67
20061128
J Cell Sci. 2009 Nov 1;122(Pt 21):3831-6
19889968
J Cell Biol. 2010 May 17;189(4):641-9
20479465
J Cell Biol. 2001 Jan 22;152(2):349-60
11266451
Cell. 2006 Dec 1;127(5):969-82
17129782
Nat Struct Mol Biol. 2007 Jan;14(1):54-9
17195848
Nature. 2005 Apr 21;434(7036):987-94
15846338
Mol Biol Cell. 2007 Oct;18(10):3800-9
17634282
Mol Cell Proteomics. 2007 Dec;6(12):2200-11
17921176
Curr Biol. 2011 Feb 8;21(3):214-20
21256022