p27KiP1 Is a Microtubule-Associated Protein that Promotes Microtubule Polymerization during Neuron Migration

被引:81
|
作者
Godin, Juliette D. [1 ,3 ]
Thomas, Noemie [1 ,3 ]
Laguesse, Sophie [1 ,3 ]
Malinouskaya, Lina [1 ,3 ]
Close, Pierre [2 ,3 ]
Malaise, Olivier [1 ,3 ]
Purnelle, Audrey [1 ,3 ]
Raineteau, Olivier [5 ]
Campbell, Kenneth [6 ]
Fero, Matthew [7 ]
Moonen, Gustave [1 ,3 ]
Malgrange, Brigitte [1 ,3 ]
Chariot, Alain [2 ,3 ]
Metin, Christine [8 ,9 ]
Besson, Arnaud [10 ]
Nguyen, Laurent [1 ,3 ,4 ]
机构
[1] Univ Liege, CHU Sart Tilman, GIGA Neurosci, B-4000 Liege, Belgium
[2] Univ Liege, CHU Sart Tilman, GIGA Signal Transduct, B-4000 Liege, Belgium
[3] Univ Liege, CHU Sart Tilman, Interdisciplinary Cluster Appl Genoprote GIGA R, B-4000 Liege, Belgium
[4] Univ Liege, CHU Sart Tilman, Wallon Excellence Lifesci & Biotechnol WELBIO, B-4000 Liege, Belgium
[5] Univ Zurich, Brain Res Inst, ETH, CH-8057 Zurich, Switzerland
[6] Childrens Hosp Res Fdn, Div Dev Neurobiol, Cincinnati, OH 45229 USA
[7] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA
[8] Hop La Pitie Salpetriere, U839, INSERM, F-75651 Paris 13, France
[9] Univ Paris 06, F-75230 Paris 05, France
[10] Univ Toulouse, CNRS Toulouse ERL5294, Canc Res Ctr Toulouse, INSERM UMR1037, Toulouse, France
关键词
DEVELOPING CEREBRAL-CORTEX; KINASE RHO-KINASE; CELL-MIGRATION; NUCLEAR TRANSLOCATION; CORTICAL INTERNEURONS; ACTIN FLOW; DLX GENES; MYOSIN; NUCLEOKINESIS; CENTROSOME;
D O I
10.1016/j.devcel.2012.08.006
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The migration of cortical interneurons is characterized by extensive morphological changes that result from successive cycles of nucleokinesis and neurite branching. Their molecular bases remain elusive, and the present work describes how p27(Kip1) controls cell-cycle-unrelated signaling pathways to regulate these morphological remodelings. Live imaging reveals that interneurons lacking p27(Kip1) show delayed tangential migration resulting from defects in both nucleokinesis and dynamic branching of the leading process. At the molecular level, p27(Kip1) is a microtubule-associated protein that promotes polymerization of microtubules in extending neurites, thereby contributing to tangential migration. Furthermore, we show that p27(Kip1) controls actomyosin contractions that drive both forward translocation of the nucleus and growth cone splitting. Thus, p27(Kip1) cell-autonomously controls nucleokinesis and neurite branching by regulating both actin and microtubule cytoskeletons.
引用
收藏
页码:729 / 744
页数:16
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