Regulation of cytoplasmic dynein behaviour and microtubule organization by mammalian Lis1

被引:322
作者
Smith, DS
Niethammer, M
Ayala, R
Zhou, Y
Gambello, MJ
Wynshaw-Boris, A
Tsai, LH
机构
[1] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA
[3] Univ Calif San Diego, Sch Med, Dept Pediat & Med, La Jolla, CA 92093 USA
关键词
D O I
10.1038/35041000
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Whereas total loss of Lis1 is lethal, disruption of one allele of the Lis1 gene results in brain abnormalities, indicating that developing neurons are particularly sensitive to a reduction in Lis1 dosage. Here we show that Lis1 is enriched in neurons relative to levels in other cell types, and that Lis1 interacts with the microtubule motor cytoplasmic dynein. Production of more Lis1 in non-neuronal cells increases retrograde movement of cytoplasmic dynein and leads to peripheral accumulation of microtubules. These changes may reflect neuron-like dynein behaviours induced by abundant Lis1. Lis1 deficiency produces the opposite phenotype. Our results indicate that abundance of Lis1 in neurons may stimulate specific dynein functions that function in neuronal migration and axon growth.
引用
收藏
页码:767 / 775
页数:9
相关论文
共 51 条
[31]   Cell cycle regulation of dynein association with membranes modulates microtubule-based organelle transport [J].
Niclas, J ;
Allan, VJ ;
Vale, RD .
JOURNAL OF CELL BIOLOGY, 1996, 133 (03) :585-593
[32]   The cdk5/p35 kinase is essential for neurite outgrowth during neuronal differentiation [J].
Nikolic, M ;
Dudek, H ;
Kwon, YT ;
Ramos, YFM ;
Tsai, LH .
GENES & DEVELOPMENT, 1996, 10 (07) :816-825
[33]   LIS1 and XLIS (DCX) mutations cause most classical lissencephaly, but different patterns of malformation [J].
Pilz, DT ;
Matsumoto, N ;
Minnerath, S ;
Mills, P ;
Gleeson, JG ;
Allen, KM ;
Walsh, CA ;
Barkovich, AJ ;
Dobyns, WB ;
Ledbetter, DH ;
Ross, ME .
HUMAN MOLECULAR GENETICS, 1998, 7 (13) :2029-2037
[34]   ER-to-Golgi transport visualized in living cells [J].
Presley, JF ;
Cole, NB ;
Schroer, TA ;
Hirschberg, K ;
Zaal, KJM ;
LippincottSchwartz, J .
NATURE, 1997, 389 (6646) :81-85
[35]   Dynactin is required for microtubule anchoring at centrosomes [J].
Quintyne, NJ ;
Gill, SR ;
Eckley, DM ;
Crego, CL ;
Compton, DA ;
Schroer, TA .
JOURNAL OF CELL BIOLOGY, 1999, 147 (02) :321-334
[36]  
Rothwell SW, 1997, THROMB HAEMOSTASIS, V78, P910
[37]   Reduction of microtubule catastrophe events by LIS1, platelet-activating factor acetylhydrolase subunit [J].
Sapir, T ;
Elbaum, M ;
Reiner, O .
EMBO JOURNAL, 1997, 16 (23) :6977-6984
[38]  
Schliwa M, 1999, BIOCHEM SOC SYMP, V65, P223
[39]  
Smith DS, 1997, J NEUROSCI, V17, P646
[40]   IN-VITRO RECONSTITUTION OF CENTROSOME ASSEMBLY AND FUNCTION - THE CENTRAL ROLE OF GAMMA-TUBULIN [J].
STEARNS, T ;
KIRSCHNER, M .
CELL, 1994, 76 (04) :623-637