The cortical protein Lte1 promotes mitotic exit by inhibiting the spindle position checkpoint kinase Kin4

被引:52
作者
Bertazzi, Daniela Trinca [1 ]
Kurtulmus, Bahtiyar [1 ]
Pereira, Gislene [1 ]
机构
[1] German Canc Res Ctr, DKFZ ZMBH Alliance, D-69120 Heidelberg, Germany
关键词
STEM-CELL DIVISION; BUDDING YEAST; SACCHAROMYCES-CEREVISIAE; NUCLEOTIDE EXCHANGE; SPATIAL REGULATION; CYCLE REGULATION; PLASMA-MEMBRANE; SHUTTLE VECTORS; ELM1; KINASE; BUD CORTEX;
D O I
10.1083/jcb.201101056
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The spindle position checkpoint (SPOC) is an essential surveillance mechanism that allows mitotic exit only when the spindle is correctly oriented along the cell axis. Key SPOC components are the kinase Kin4 and the Bub2-Bfa1 GAP complex that inhibit the mitotic exit-promoting GTPase Tem1. During an unperturbed cell cycle, Kin4 associates with the mother spindle pole body (mSPB), whereas Bub2-Bfa1 is at the daughter SPB (dSPB). When the spindle is mispositioned, Bub2-Bfa1 and Kin4 bind to both SPBs, which enables Kin4 to phosphorylate Bfa1 and thereby block mitotic exit. Here, we show that the daughter cell protein Lte1 physically interacts with Kin4 and inhibits Kin4 kinase activity. Specifically, Lte1 binds to catalytically active Kin4 and promotes Kin4 hyperphosphorylation, which restricts Kin4 binding to the mSPB. This Lte1-mediated exclusion of Kin4 from the dSPB is essential for proper mitotic exit of cells with a correctly aligned spindle. Therefore, Lte1 promotes mitotic exit by inhibiting Kin4 activity at the dSPB.
引用
收藏
页码:1033 / 1048
页数:16
相关论文
共 63 条
[21]   Nud1p links astral microtubule organization and the control of exit from mitosis [J].
Gruneberg, U ;
Campbell, K ;
Simpson, C ;
Grindlay, J ;
Schiebel, E .
EMBO JOURNAL, 2000, 19 (23) :6475-6488
[22]   Novel regulation of mitotic exit by the Cdc42 effectors Gic1 and Gic2 [J].
Höfken, T ;
Schiebel, E .
JOURNAL OF CELL BIOLOGY, 2004, 164 (02) :219-231
[23]   A role for cell polarity proteins in mitotic exit [J].
Höfken, T ;
Schiebel, E .
EMBO JOURNAL, 2002, 21 (18) :4851-4862
[24]   Regulation of the Bub2/Bfal GAP complex by Cdc5 and cell cycle checkpoints [J].
Hu, FH ;
Wang, YC ;
Liu, D ;
Li, YM ;
Qin, J ;
Elledge, SJ .
CELL, 2001, 107 (05) :655-665
[25]   E-Cadherin Is Required for Centrosome and Spindle Orientation in Drosophila Male Germline Stem Cells [J].
Inaba, Mayu ;
Yuan, Hebao ;
Salzmann, Viktoria ;
Fuller, Margaret T. ;
Yamashita, Yukiko M. .
PLOS ONE, 2010, 5 (08)
[26]   A versatile toolbox for PCR-based tagging of yeast genes: new fluorescent proteins, more markers and promoter substitution cassettes [J].
Janke, C ;
Magiera, MM ;
Rathfelder, N ;
Taxis, C ;
Reber, S ;
Maekawa, H ;
Moreno-Borchart, A ;
Doenges, G ;
Schwob, E ;
Schiebel, E ;
Knop, M .
YEAST, 2004, 21 (11) :947-962
[27]   Cdc14 activates Cdc15 to promote mitotic exit in budding yeast [J].
Jaspersen, SL ;
Morgan, DO .
CURRENT BIOLOGY, 2000, 10 (10) :615-618
[28]   Spatial regulation of the guanine nucleotide exchange factor Lte1 in Saccharomyces cerevisiae [J].
Jensen, S ;
Geymonat, M ;
Johnson, AL ;
Segal, M ;
Johnston, LH .
JOURNAL OF CELL SCIENCE, 2002, 115 (24) :4977-4991
[29]   LTE1 OF SACCHAROMYCES-CEREVISIAE IS A 1435-CODON OPEN READING FRAME THAT HAS SEQUENCE SIMILARITIES TO GUANINE-NUCLEOTIDE RELEASING FACTORS [J].
KENG, T ;
CLARK, MW ;
STORMS, RK ;
FORTIN, N ;
ZHONG, WW ;
OUELLETTE, BFF ;
BARTON, AB ;
KABACK, DB ;
BUSSEY, H .
YEAST, 1994, 10 (07) :953-958
[30]   Phosphorylation-Dependent Protein Interactions at the Spindle Midzone Mediate Cell Cycle Regulation of Spindle Elongation [J].
Khmelinskii, Anton ;
Roostalu, Johanna ;
Roque, Helio ;
Antony, Claude ;
Schiebel, Elmar .
DEVELOPMENTAL CELL, 2009, 17 (02) :244-256