한빛사논문
- 조회1,999
Abstract
Doogie Oha,b,c,1, Che-Hang Yua, and Daniel J. Needlemana,b,c,1
aJohn A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138;
bDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138;
cFaculty of Arts and Sciences Center for Systems Biology, Harvard University, Cambridge, MA 02138
Abstract
Concentration gradients of soluble proteins are believed to be responsible for control of morphogenesis of subcellular systems, but the mechanisms that generate the spatial organization of these subcellular gradients remain poorly understood. Here, we use a newly developed multipoint fluorescence fluctuation spectroscopy technique to study the ras-related nuclear protein (Ran) pathway, which forms soluble gradients around chromosomes in mitosis and is thought to spatially regulate microtubule behaviors during spindle assembly. We found that the distribution of components of the Ran pathway that influence microtubule behaviors is determined by their interactions with microtubules, resulting in microtubule nucleators being localized by the microtubules whose formation they stimulate. Modeling and perturbation experiments show that this feedback makes the length of the spindle insensitive to the length scale of the Ran gradient, allows the spindle to assemble outside the peak of the Ran gradient, and explains the scaling of the spindle with cell size. Such feedback between soluble signaling pathways and the mechanics of the cytoskeleton may be a general feature of subcellular organization.
RanGTP gradient, spatial organization, microtubule nucleation, feedback loop, spindle size
1To whom correspondence may be addressed.
Author contributions: D.O. and D.J.N. designed research; D.O. performed research; C.-H.Y. contributed new reagents/analytic tools; D.O. and D.J.N. analyzed data; and D.O. and D.J.N. wrote the paper.
논문정보
- Research article
- 2016년 07월 (BRIC 등록일 2016-07-25)
- 국외 연구진
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