Spencer Alison K, Schaumberg Andrew J, Zallen Jennifer A
Gerstner Sloan Kettering Graduate School of Biomedical Sciences.
Howard Hughes Medical Institute and Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065.
Mol Biol Cell. 2017 Jun 1;28(11):1519-1529. doi: 10.1091/mbc.E16-10-0691. Epub 2017 Apr 12.
Spatially organized macromolecular complexes are essential for cell and tissue function, but the mechanisms that organize micron-scale structures within cells are not well understood. Microtubule-based structures such as mitotic spindles scale with cell size, but less is known about the scaling of actin structures within cells. Actin-rich denticle precursors cover the ventral surface of the embryo and larva and provide templates for cuticular structures involved in larval locomotion. Using quantitative imaging and statistical modeling, we demonstrate that denticle number and spacing scale with cell length over a wide range of cell sizes in embryos and larvae. Denticle number and spacing are reduced under space-limited conditions, and both features robustly scale over a 10-fold increase in cell length during larval growth. We show that the relationship between cell length and denticle spacing can be recapitulated by specific mathematical equations in embryos and larvae and that accurate denticle spacing requires an intact microtubule network and the microtubule minus end-binding protein, Patronin. These results identify a novel mechanism of micro-tubule-dependent actin scaling that maintains precise patterns of actin organization during tissue growth.
空间组织的大分子复合物对于细胞和组织功能至关重要,但细胞内微米级结构的组织机制尚不清楚。基于微管的结构,如有丝分裂纺锤体,会随着细胞大小而缩放,但对于细胞内肌动蛋白结构的缩放了解较少。富含肌动蛋白的齿状突起前体覆盖胚胎和幼虫的腹面,并为参与幼虫运动的表皮结构提供模板。通过定量成像和统计建模,我们证明在胚胎和幼虫中,在广泛的细胞大小范围内,齿状突起的数量和间距随细胞长度而缩放。在空间有限的条件下,齿状突起的数量和间距会减少,并且在幼虫生长过程中,这两个特征在细胞长度增加10倍的情况下仍能稳健地缩放。我们表明,胚胎和幼虫中细胞长度与齿状突起间距之间的关系可以通过特定的数学方程来概括,并且精确的齿状突起间距需要完整的微管网络和微管负端结合蛋白Patronin。这些结果确定了一种新的微管依赖性肌动蛋白缩放机制,该机制在组织生长过程中维持肌动蛋白组织的精确模式。