Clathrin is required for the function of the mitotic spindle

被引:208
作者
Royle, SJ
Bright, NA
Lagnado, L
机构
[1] MRC, Mol Biol Lab, Cambridge CB2 2QH, England
[2] Univ Cambridge, Addenbrookes Hosp, Cambridge Inst Med Res, Cambridge CB2 2XY, England
[3] Univ Cambridge, Addenbrookes Hosp, Dept Clin Biochem, Cambridge CB2 2XY, England
基金
英国医学研究理事会;
关键词
D O I
10.1038/nature03502
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
Clathrin has an established function in the generation of vesicles that transfer membrane and proteins around the cell(1-4). The formation of clathrin-coated vesicles occurs continuously in nondividing cells(5), but is shut down during mitosis(6), when clathrin concentrates at the spindle apparatus(7,8). Here, we show that clathrin stabilizes fibres of the mitotic spindle to aid congression of chromosomes. Clathrin bound to the spindle directly by the amino-terminal domain of clathrin heavy chain. Depletion of clathrin heavy chain using RNA interference prolonged mitosis; kinetochore fibres were destabilized, leading to defective congression of chromosomes to the metaphase plate and persistent activation of the spindle checkpoint. Normal mitosis was rescued by clathrin triskelia but not the N-terminal domain of clathrin heavy chain, indicating that stabilization of kinetochore fibres was dependent on the unique structure of clathrin. The importance of clathrin for normal mitosis may be relevant to understanding human cancers that involve gene fusions of clathrin heavy chain.
引用
收藏
页码:1152 / 1157
页数:6
相关论文
共 30 条
[1]   A novel CLTC-TFE3 gene fusion in pediatric renal adenocarcinoma with t(X;17)(p11.2;q23) [J].
Argani, P ;
Lui, MY ;
Couturier, J ;
Bouvier, R ;
Fournet, JC ;
Ladanyi, M .
ONCOGENE, 2003, 22 (34) :5374-5378
[2]   P2X receptor trafficking in neurons is subunit specific [J].
Bobanovic, LK ;
Royle, SJ ;
Murrell-Lagnado, RD .
JOURNAL OF NEUROSCIENCE, 2002, 22 (12) :4814-4824
[3]  
Bright NA, 1997, J CELL SCI, V110, P2027
[4]   Biological basket weaving: Formation and function of clathrin-coated vesicles [J].
Brodsky, FM ;
Chen, CY ;
Knuehl, C ;
Towler, MC ;
Wakeham, DE .
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 2001, 17 :517-568
[5]   Centromeres and kinetochores: From epigenetics to mitotic checkpoint signaling [J].
Cleveland, DW ;
Mao, YH ;
Sullivan, KF .
CELL, 2003, 112 (04) :407-421
[6]   Spindle assembly in animal cells [J].
Compton, DA .
ANNUAL REVIEW OF BIOCHEMISTRY, 2000, 69 :95-114
[7]   Molecular model for a complete clathrin lattice from electron cryomicroscopy [J].
Fotin, A ;
Cheng, YF ;
Sliz, P ;
Grigorieff, N ;
Harrison, SC ;
Kirchhausen, T ;
Walz, T .
NATURE, 2004, 432 (7017) :573-579
[8]   Spatial control of coated-pit dynamics in living cells [J].
Gaidarov, I ;
Santini, F ;
Warren, RA ;
Keen, JH .
NATURE CELL BIOLOGY, 1999, 1 (01) :1-7
[9]   INTERMICROTUBULE BRIDGES IN MITOTIC SPINDLE APPARATUS [J].
HEPLER, PK ;
MCINTOSH, JR ;
CLELAND, S .
JOURNAL OF CELL BIOLOGY, 1970, 45 (02) :438-+
[10]   Effect of clathrin heavy chain- and α-adaptin-specific small inhibitory RNAs on endocytic accessory proteins and receptor trafficking in HeLa cells [J].
Hinrichsen, L ;
Harborth, J ;
Andrees, L ;
Weber, K ;
Ungewickell, EJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (46) :45160-45170