The minus-end depolymerase KIF2A drives flux-like treadmilling of γTuRC-uncapped microtubules.
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
02 10 2023
02 10 2023
Historique:
received:
05
04
2023
revised:
27
07
2023
accepted:
04
08
2023
medline:
25
8
2023
pubmed:
24
8
2023
entrez:
24
8
2023
Statut:
ppublish
Résumé
During mitosis, microtubules in the spindle turn over continuously. At spindle poles, where microtubule minus ends are concentrated, microtubule nucleation and depolymerization, the latter required for poleward microtubule flux, happen side by side. How these seemingly antagonistic processes of nucleation and depolymerization are coordinated is not understood. Here, we reconstitute this coordination in vitro combining different pole-localized activities. We find that the spindle pole-localized kinesin-13 KIF2A is a microtubule minus-end depolymerase, in contrast to its paralog MCAK. Due to its asymmetric activity, KIF2A still allows microtubule nucleation from the γ-tubulin ring complex (γTuRC), which serves as a protective cap shielding the minus end against KIF2A binding. Efficient γTuRC uncapping requires the combined action of KIF2A and a microtubule severing enzyme, leading to treadmilling of the uncapped microtubule driven by KIF2A. Together, these results provide insight into the molecular mechanisms by which a minimal protein module coordinates microtubule nucleation and depolymerization at spindle poles consistent with their role in poleward microtubule flux.
Identifiants
pubmed: 37615667
pii: 276200
doi: 10.1083/jcb.202304020
pmc: PMC10450741
pii:
doi:
Substances chimiques
Kinesins
EC 3.6.4.4
KIF2A protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Cancer Research UK
ID : FC001163
Pays : United Kingdom
Organisme : Arthritis Research UK
ID : FC001163
Pays : United Kingdom
Organisme : Medical Research Council
ID : FC001163
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC001163
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
© 2023 Henkin et al.
Références
Science. 1997 Jan 10;275(5297):215-8
pubmed: 8985015
Dev Cell. 2020 Jun 8;53(5):603-617.e8
pubmed: 32433913
J Cell Biol. 2006 Apr 24;173(2):173-9
pubmed: 16636143
Cell. 1978 Jan;13(1):1-8
pubmed: 620419
J Cell Sci. 2006 Oct 1;119(Pt 19):3905-13
pubmed: 16988025
Proc Natl Acad Sci U S A. 2020 Jun 9;117(23):12847-12855
pubmed: 32457163
Biochem Soc Trans. 2018 Dec 17;46(6):1665-1672
pubmed: 30467119
Cell. 2018 Oct 18;175(3):796-808.e14
pubmed: 30340043
J Cell Sci. 2006 Jun 1;119(Pt 11):2354-61
pubmed: 16723741
J Cell Sci. 2012 Jun 1;125(Pt 11):2561-9
pubmed: 22595526
Curr Biol. 2019 Jul 8;29(13):2120-2130.e7
pubmed: 31231047
Mol Biol Cell. 2009 Nov;20(22):4696-705
pubmed: 19793918
Protein Expr Purif. 2003 Nov;32(1):83-8
pubmed: 14680943
Nat Commun. 2018 Jul 6;9(1):2628
pubmed: 29980677
Semin Cell Dev Biol. 2021 Sep;117:99-117
pubmed: 34053864
Nat Rev Mol Cell Biol. 2015 Dec;16(12):711-26
pubmed: 26562752
Dev Cell. 2020 Jan 6;52(1):118-131.e6
pubmed: 31735665
Semin Cell Dev Biol. 2010 May;21(3):276-82
pubmed: 20109574
Cell Cycle. 2006 Aug;5(16):1812-5
pubmed: 16929184
J Cell Sci. 2019 Jan 14;132(4):
pubmed: 30578316
J Cell Biol. 2004 Aug 16;166(4):473-8
pubmed: 15302853
Nat Struct Mol Biol. 2017 Nov;24(11):931-943
pubmed: 28991265
Cell. 1999 Jan 8;96(1):69-78
pubmed: 9989498
Cell Rep. 2022 Aug 2;40(5):111169
pubmed: 35926461
J Cell Biol. 1989 Aug;109(2):637-52
pubmed: 2760109
J Cell Biol. 2021 Mar 1;220(3):
pubmed: 33496729
Science. 2003 Jun 13;300(5626):1715-8
pubmed: 12714675
Mol Cell. 2002 Apr;9(4):903-9
pubmed: 11983180
J Cell Biol. 2007 Apr 23;177(2):231-42
pubmed: 17452528
Biophys J. 2015 Dec 15;109(12):2546-2561
pubmed: 26682813
Cell. 2010 Oct 15;143(2):263-74
pubmed: 20946984
Proc Natl Acad Sci U S A. 2019 Mar 19;116(12):5533-5541
pubmed: 30837315
J Biol Chem. 2001 Sep 14;276(37):34753-8
pubmed: 11466324
Nat Cell Biol. 2017 May;19(5):480-492
pubmed: 28436967
Structure. 2008 Nov 12;16(11):1732-9
pubmed: 19000825
J Cell Biol. 2021 Aug 2;220(8):
pubmed: 34137788
Biol Open. 2020 Dec 1;9(11):
pubmed: 33168591
Mol Biol Cell. 2012 Dec;23(24):4786-95
pubmed: 23087211
J Cell Biol. 2021 Aug 2;220(8):
pubmed: 34137789
J Cell Biol. 2016 Nov 7;215(3):357-368
pubmed: 27799364
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
EMBO J. 2020 Dec 1;39(23):e105432
pubmed: 33073400
Mol Biol Cell. 2006 Feb;17(2):700-10
pubmed: 16291860
J Cell Biol. 2010 May 3;189(3):465-80
pubmed: 20439998
Science. 2018 Aug 24;361(6404):
pubmed: 30139843
J Cell Biol. 2013 Aug 19;202(4):623-36
pubmed: 23960144
Curr Biol. 2010 Oct 12;20(19):1717-22
pubmed: 20850319
J Cell Sci. 1996 Mar;109 ( Pt 3):561-7
pubmed: 8907702
Curr Biol. 2005 Oct 25;15(20):1827-32
pubmed: 16243029
Exp Cell Res. 2005 Oct 1;309(2):358-69
pubmed: 16026783
Nature. 1984 Nov 15-21;312(5991):237-42
pubmed: 6504138
Elife. 2022 Jul 27;11:
pubmed: 35894209
Mol Biol Cell. 2007 Oct;18(10):3993-4002
pubmed: 17671163
Structure. 2019 Mar 5;27(3):497-506.e4
pubmed: 30661854
Nat Rev Mol Cell Biol. 2011 Oct 12;12(11):709-21
pubmed: 21993292
Mol Cell. 2003 Feb;11(2):445-57
pubmed: 12620232
Nat Mater. 2015 Nov;14(11):1156-63
pubmed: 26343914
Biophys J. 2001 Jul;81(1):66-78
pubmed: 11423395
Nature. 2006 May 4;441(7089):115-9
pubmed: 16672973
J Cell Biol. 2004 Aug 16;166(4):465-71
pubmed: 15314063
Cell. 1991 Feb 22;64(4):827-39
pubmed: 1671762
Curr Biol. 2005 Apr 12;15(7):650-5
pubmed: 15823537
Nat Methods. 2017 Jan;14(1):53-56
pubmed: 27869816
Elife. 2020 Jun 15;9:
pubmed: 32538784
Nat Biotechnol. 2004 Dec;22(12):1567-72
pubmed: 15558047
Mol Biol Cell. 2023 Jan 1;34(1):ar1
pubmed: 36350698
J Cell Biol. 2006 Oct 9;175(1):25-31
pubmed: 17015621
Annu Rev Cell Dev Biol. 1997;13:83-117
pubmed: 9442869
Nat Rev Mol Cell Biol. 2021 Dec;22(12):777-795
pubmed: 34408299
J Cell Sci. 2005 Mar 15;118(Pt 6):1105-16
pubmed: 15764594
Proc Natl Acad Sci U S A. 2012 Jul 24;109(30):12011-6
pubmed: 22778434
Elife. 2013 Feb 19;2:e00290
pubmed: 23425906
PLoS One. 2013 Aug 28;8(8):e73075
pubmed: 24015286
J Cell Biol. 2023 Mar 6;222(3):
pubmed: 36695784
EMBO J. 2023 Jun 1;42(11):e112953
pubmed: 37014312
J Cell Biol. 1997 Oct 20;139(2):417-34
pubmed: 9334345
Mol Biol Cell. 2007 Aug;18(8):2970-9
pubmed: 17538014
Cell Rep. 2013 Mar 28;3(3):759-68
pubmed: 23434508
Nat Commun. 2017 Jul 10;8(1):70
pubmed: 28694425
Nature. 2008 Jan 17;451(7176):363-7
pubmed: 18202664
J Cell Sci. 2019 Jun 7;132(11):
pubmed: 31175152
Nature. 2004 Jan 22;427(6972):364-70
pubmed: 14681690
J Cell Biol. 2007 Dec 3;179(5):869-79
pubmed: 18039936
Nat Commun. 2018 Apr 25;9(1):1662
pubmed: 29695795
Essays Biochem. 2018 Dec 7;62(6):765-780
pubmed: 30315097
Cell. 2011 Nov 23;147(5):1092-103
pubmed: 22118464
Methods Mol Biol. 2022;2430:315-336
pubmed: 35476342