Phosphatidylinositol-5-phosphate 4-kinase gamma accumulates at the spindle pole and prevents microtubule depolymerization.
Microtubule depolymerization
Mitotic centromere-associated kinesin (MCAK)
Phosphatidylinositol 4,5-bisphosphate (PIP2)
Phosphatidylinositol 5-phosphate 4-kinase type II gamma (PIP4KIIγ)
Polo-like kinase (PLK1)
Spindle pole
Journal
Cell division
ISSN: 1747-1028
Titre abrégé: Cell Div
Pays: England
ID NLM: 101251560
Informations de publication
Date de publication:
2019
2019
Historique:
received:
05
05
2019
accepted:
13
08
2019
entrez:
28
8
2019
pubmed:
28
8
2019
medline:
28
8
2019
Statut:
epublish
Résumé
A previous screen of a human kinase and phosphatase shRNA library to select genes that mediate arsenite induction of spindle abnormalities resulted in the identification of phosphatidylinositol-5-phosphate 4-kinase type-2 gamma (PIP4KIIγ), a phosphatidylinositol 4,5-bisphosphate (PIP2)-synthesizing enzyme. In this study, we explored how PIP4KIIγ regulates the assembly of mitotic spindles. PIP4KIIγ accumulates at the spindle pole before anaphase, and is required for the assembly of functional bipolar spindles. Depletion of PIP4KIIγ enhanced the spindle pole accumulation of mitotic centromere-associated kinesin (MCAK), a microtubule (MT)-depolymerizing kinesin, and resulted in a less stable spindle pole-associated MT. Depletion of MCAK can ameliorate PIP4KIIγ depletion-induced spindle abnormalities. In addition, PIP2 binds to polo-like kinase (PLK1) and reduces PLK1-mediated phosphorylation of MCAK. These results indicate that PIP4KIIγ and PIP2 may negatively regulate the MT depolymerization activity of MCAK by reducing PLK1-mediated phosphorylation of MCAK. Consequently, depletion of PLK1 has been shown to counteract the PIP4KIIγ depletion-induced instability of spindle pole-associated MT and cell resistance to arsenite. Our current results imply that PIP4KIIγ may restrain MT depolymerization at the spindle pole through attenuating PLK1-mediated activation of MCAK before anaphase onset.
Sections du résumé
BACKGROUND
BACKGROUND
A previous screen of a human kinase and phosphatase shRNA library to select genes that mediate arsenite induction of spindle abnormalities resulted in the identification of phosphatidylinositol-5-phosphate 4-kinase type-2 gamma (PIP4KIIγ), a phosphatidylinositol 4,5-bisphosphate (PIP2)-synthesizing enzyme. In this study, we explored how PIP4KIIγ regulates the assembly of mitotic spindles.
RESULTS
RESULTS
PIP4KIIγ accumulates at the spindle pole before anaphase, and is required for the assembly of functional bipolar spindles. Depletion of PIP4KIIγ enhanced the spindle pole accumulation of mitotic centromere-associated kinesin (MCAK), a microtubule (MT)-depolymerizing kinesin, and resulted in a less stable spindle pole-associated MT. Depletion of MCAK can ameliorate PIP4KIIγ depletion-induced spindle abnormalities. In addition, PIP2 binds to polo-like kinase (PLK1) and reduces PLK1-mediated phosphorylation of MCAK. These results indicate that PIP4KIIγ and PIP2 may negatively regulate the MT depolymerization activity of MCAK by reducing PLK1-mediated phosphorylation of MCAK. Consequently, depletion of PLK1 has been shown to counteract the PIP4KIIγ depletion-induced instability of spindle pole-associated MT and cell resistance to arsenite.
CONCLUSIONS
CONCLUSIONS
Our current results imply that PIP4KIIγ may restrain MT depolymerization at the spindle pole through attenuating PLK1-mediated activation of MCAK before anaphase onset.
Identifiants
pubmed: 31452676
doi: 10.1186/s13008-019-0053-9
pii: 53
pmc: PMC6702725
doi:
Types de publication
Journal Article
Langues
eng
Pagination
9Déclaration de conflit d'intérêts
Competing interestsThe authors declare that they have no competing interests.
Références
J Neurosci. 2002 Mar 1;22(5):1668-78
pubmed: 11880496
Mol Pharmacol. 2002 Sep;62(3):529-38
pubmed: 12181429
Mol Cell. 2003 Feb;11(2):445-57
pubmed: 12620232
J Membr Biol. 2003 Jul 15;194(2):77-89
pubmed: 14502432
Proc Natl Acad Sci U S A. 2004 Feb 10;101(6):1584-8
pubmed: 14747658
Curr Biol. 2004 Feb 17;14(4):273-86
pubmed: 14972678
J Biol Chem. 2005 Feb 25;280(8):6897-905
pubmed: 15579910
Mol Cell Biol. 2005 Mar;25(5):2031-44
pubmed: 15713655
Mol Biol Cell. 2006 Apr;17(4):1946-58
pubmed: 16436516
Cell Cycle. 2006 Mar;5(5):481-5
pubmed: 16552178
Biochim Biophys Acta. 2006 May-Jun;1761(5-6):560-9
pubmed: 16750654
Mol Biol Cell. 2007 Aug;18(8):3094-104
pubmed: 17553931
Int Rev Cytol. 2008;265:111-58
pubmed: 18275887
J Cell Sci. 2008 Apr 1;121(Pt 7):1076-84
pubmed: 18334551
Dev Cell. 2008 May;14(5):646-59
pubmed: 18477449
Mol Cell. 2008 Aug 8;31(3):438-48
pubmed: 18691976
Dev Cell. 2008 Aug;15(2):198-208
pubmed: 18694560
Development. 2008 Dec;135(23):3829-38
pubmed: 18948416
J Cell Sci. 2009 Nov 1;122(Pt 21):3837-50
pubmed: 19889969
Semin Cell Dev Biol. 2010 May;21(3):276-82
pubmed: 20109574
Nat Rev Cancer. 2010 May;10(5):342-52
pubmed: 20414202
Cell Mol Life Sci. 2010 Dec;67(23):3927-46
pubmed: 20559679
Mol Cell Proteomics. 2011 Feb;10(2):M110.003376
pubmed: 21048195
J Biol Chem. 2011 Jan 28;286(4):3033-46
pubmed: 21078677
J Biol Chem. 2011 Oct 21;286(42):36378-84
pubmed: 21903575
Oncotarget. 2011 Dec;2(12):935-47
pubmed: 22249213
Proc Natl Acad Sci U S A. 2012 Jan 31;109(5):1725-30
pubmed: 22307638
Genetics. 2012 Apr;190(4):1197-224
pubmed: 22491889
Toxicol Sci. 2012 Jul;128(1):115-25
pubmed: 22496355
Toxicol Sci. 2012 Jul;128(1):126-36
pubmed: 22496356
J Cell Sci. 2012 Jun 15;125(Pt 12):2805-14
pubmed: 22736044
Nat Struct Mol Biol. 2013 Sep;20(9):1047-53
pubmed: 23893132
J Cell Sci. 2014 Mar 15;127(Pt 6):1293-305
pubmed: 24434581
Nucleic Acids Res. 2015 Jan;43(Database issue):D328-34
pubmed: 25392421
Oncotarget. 2015 Mar 30;6(9):6641-55
pubmed: 25504441
Oncogene. 2015 Sep 10;34(37):4799-807
pubmed: 25619835
Exp Cell Res. 2015 May 15;334(1):61-9
pubmed: 25708751
Oncotarget. 2015 Nov 3;6(34):36472-88
pubmed: 26472023
Cell Mol Life Sci. 2016 Oct;73(20):3949-60
pubmed: 27137183
Chromosoma. 1981;84(1):145-58
pubmed: 7297248
Carcinogenesis. 1998 May;19(5):889-96
pubmed: 9635879