Model for anaphase B: Role of three mitotic motors in a switch from poleward flux to spindle elongation

被引:114
作者
Brust-Mascher, I [1 ]
Civelekoglu-Scholey, G [1 ]
Kwon, M [1 ]
Mogilner, A [1 ]
Scholey, JM [1 ]
机构
[1] Univ Calif Davis, Ctr Genet & Dev, Lab Cell & Computat Biol, Davis, CA 95616 USA
关键词
D O I
10.1073/pnas.0407044101
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
It has been proposed that the suppression of poleward flux within interpolar microtubule (ipMT) bundles of Drosophila embryonic spindles couples outward forces generated by a sliding filament mechanism to anaphase spindle elongation. Here, we (i) propose a molecular mechanism in which the bipolar kinesin KLP61F persistently slides dynamically unstable ipMTs outward, the MT depolymerase KLP10A acts at the poles to convert ipMT sliding to flux, and the chromokinesin KLP3A inhibits the depolymerase to suppress flux, thereby coupling ipMT sliding to spindle elongation; (ii) used KLP3A inhibitors to interfere with the coupling process, which revealed an inverse linear relation between the rates of flux and elongation, supporting the proposed mechanism and demonstrating that the suppression of flux controls both the rate and onset of spindle elongation; and (iii) developed a mathematical model using force balance and rate equations to describe how motors sliding the highly dynamic ipMTs apart can drive spindle elongation at a steady rate determined by the extent of suppression of flux.
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页码:15938 / 15943
页数:6
相关论文
共 26 条
[1]   Microtubule flux and sliding in mitotic spindles of Drosophila embryos [J].
Brust-Mascher, I ;
Scholey, JM .
MOLECULAR BIOLOGY OF THE CELL, 2002, 13 (11) :3967-3975
[2]  
COHN SA, 1988, EUR J CELL BIOL, V46, P523
[3]  
COLE DG, 1994, J BIOL CHEM, V269, P22913
[4]   Dynein/dynactin regulate metaphase spindle length by targeting depolymerizing activities to spindle poles [J].
Gaetz, J ;
Kapoor, TM .
JOURNAL OF CELL BIOLOGY, 2004, 166 (04) :465-471
[5]   INHIBITION OF ANAPHASE SPINDLE ELONGATION IN-VITRO BY A PEPTIDE ANTIBODY THAT RECOGNIZES KINESIN MOTOR DOMAIN [J].
HOGAN, CJ ;
WEIN, H ;
WORDEMAN, L ;
SCHOLEY, JM ;
SAWIN, KE ;
CANDE, WZ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (14) :6611-6615
[6]   The chromokinesin, KLP3A, drives mitotic spindle pole separation during prometaphase and anaphase and facilitates chromatid motility [J].
Kwon, M ;
Morales-Mulia, S ;
Brust-Mascher, I ;
Rogers, GC ;
Sharp, DJ ;
Scholey, JM .
MOLECULAR BIOLOGY OF THE CELL, 2004, 15 (01) :219-233
[7]   A standardized kinesin nomenclature [J].
Lawrence, CJ ;
Dawe, RK ;
Christie, KR ;
Cleveland, DW ;
Dawson, SC ;
Endow, SA ;
Goldstein, LSB ;
Goodson, HV ;
Hirokawa, N ;
Howard, J ;
Malmberg, RL ;
McIntosh, JR ;
Miki, H ;
Mitchison, TJ ;
Okada, Y ;
Reddy, ASN ;
Saxton, WM ;
Schliwa, M ;
Scholey, JM ;
Vale, RD ;
Walczak, CE ;
Wordeman, L .
JOURNAL OF CELL BIOLOGY, 2004, 167 (01) :19-22
[8]   Poleward microtubule flux is a major component of spindle dynamics and anaphase A in mitotic Drosophila embryos [J].
Maddox, P ;
Desai, A ;
Oegema, K ;
Mitchison, TJ ;
Salmon, ED .
CURRENT BIOLOGY, 2002, 12 (19) :1670-1674
[9]   MITOTIC MECHANISM BASED ON INTRINSIC MICROTUBULE BEHAVIOR [J].
MARGOLIS, RL ;
WILSON, L ;
KIEFER, BI .
NATURE, 1978, 272 (5652) :450-452
[10]   INTERPOLAR SPINDLE MICROTUBULES IN PTK CELLS [J].
MASTRONARDE, DN ;
MCDONALD, KL ;
DING, R ;
MCINTOSH, JR .
JOURNAL OF CELL BIOLOGY, 1993, 123 (06) :1475-1489