Asymmetric localization of the adaptor protein Miranda in neuroblasts is achieved by diffusion and sequential interaction of Myosin II and VI

被引:20
作者
Erben, Veronika [4 ,5 ]
Waldhuber, Markus [1 ,4 ,5 ]
Langer, Diana [4 ,5 ]
Fetka, Ingrid [4 ,5 ]
Jansen, Ralf Peter [4 ,5 ]
Petritsch, Claudia [1 ,2 ,3 ,4 ,5 ]
机构
[1] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Brain Tumor Res Ctr, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Helen Diller Comprehens Canc Ctr, San Francisco, CA 94143 USA
[4] Univ Munich, Dept Biochem, Genectr, D-81377 Munich, Germany
[5] Univ Munich, Mol Biol Lab, D-81377 Munich, Germany
关键词
mechanism for asymmetric cell division; stem cells; Miranda; PON; Myosin II and VI;
D O I
10.1242/jcs.020024
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The adaptor protein Miranda plays a pivotal role in the asymmetric cell division of neuroblasts by asymmetrically segregating key differentiation factors. Miranda localization requires Myosin VI and Myosin II. The apical-then-basal localization pattern of Miranda detected in fixed tissue, and the localization defects in embryos lacking Myosin VI, suggest that Miranda is transported to the basal pole as a Myosin VI cargo. However, the mode and temporal sequence of Miranda localization have not been characterized in live embryos. Furthermore, it is unknown whether Miranda and PON, a second adaptor protein required for asymmetric protein localization, are both regulated by Myosin II. By combining immunofluorescence studies with time-lapse confocal microscopy, we show that Miranda protein forms an apical crescent at interphase, but is ubiquitously localized at prophase in a Myosin-II-dependent manner. FRAP analysis revealed that Miranda protein reaches the basal cortex by passive diffusion throughout the cell, rather than by long-range Myosin VI-directed transport. Myosin VI acts downstream of Myosin II in the same pathway to deliver diffusing Miranda to the basal cortex. PON localization occurs mainly along the cortex and requires Myosin II but not Myosin VI, suggesting that distinct mechanisms are employed to localize different adaptor proteins during asymmetric cell division.
引用
收藏
页码:1403 / 1414
页数:12
相关论文
共 38 条
[11]   Rotation and asymmetry of the mitotic spindle direct asymmetric cell division in the developing central nervous system [J].
Kaltschmidt, JA ;
Davidson, CM ;
Brown, NH ;
Brand, AH .
NATURE CELL BIOLOGY, 2000, 2 (01) :7-12
[12]   Brat is a Miranda cargo protein that promotes neuronal differentiation and inhibits neuroblast self-renewal [J].
Lee, CY ;
Wilkinson, BD ;
Siegrist, SE ;
Wharton, RP ;
Doe, CQ .
DEVELOPMENTAL CELL, 2006, 10 (04) :441-449
[13]   Partner of numb colocalizes with numb during mitosis and directs numb asymmetric localization in Drosophila neural and muscle progenitors [J].
Lu, BW ;
Rothenberg, M ;
Jan, LY ;
Jan, YN .
CELL, 1998, 95 (02) :225-235
[14]   Modes of protein movement that lead to the asymmetric localization of partner of numb during Drosophila neuroblast division [J].
Lu, BW ;
Ackerman, L ;
Jan, LY ;
Jan, YN .
MOLECULAR CELL, 1999, 4 (06) :883-891
[15]  
Matsuzaki F, 1998, DEVELOPMENT, V125, P4089
[16]   Quantitative analysis of protein dynamics during asymmetric cell division [J].
Mayer, B ;
Emery, G ;
Berdnik, D ;
Wirtz-Peitz, F ;
Knoblich, JA .
CURRENT BIOLOGY, 2005, 15 (20) :1847-1854
[17]   Miranda, a protein involved in neuroblast asymmetric division, is associated with embryonic centrosomes of Drosophila melanogaster [J].
Mollinari, C ;
Lange, B ;
González, C .
BIOLOGY OF THE CELL, 2002, 94 (01) :1-13
[18]   The Drosophila DIAP1 protein is required to prevent accumulation of a continuously generated, processed form of the apical caspase DRONC [J].
Muro, I ;
Hay, BA ;
Clem, RJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (51) :49644-49650
[19]   Persistent expression of genes of the Enhancer of split complex suppresses neural development in Drosophila [J].
Nakao, K ;
CamposOrtega, JA .
NEURON, 1996, 16 (02) :275-286
[20]   Role of cortical tumour-suppressor proteins in asymmetric division of Drosophila neuroblast [J].
Ohshiro, T ;
Yagami, T ;
Zhang, C ;
Matsuzaki, F .
NATURE, 2000, 408 (6812) :593-596