A method for multiprotein assembly in cells reveals independent action of kinesins in complex.
A method for multiprotein assembly in cells reveals independent action of kinesins in complex.
复制标题
细胞中多蛋白组装的方法揭示了复合物中驱动蛋白的独立作用。
DOI：
10.1083/jcb.201407086
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Verhey,KristenJ
中科院分区：
文献类型：
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作者：
Norris,StephenR;Soppina,Virupakshi;Dizaji,AslanS;Schimert,KristinI;Sept,David;Cai,Dawen;Sivaramakrishnan,Sivaraj;Verhey,KristenJ
Processive molecular motors such as kinesin and dynein hydrolyze ATP to walk on polarized microtubule (MT) tracks in eukaryotic cells. These motors are largely responsible for the trafficking and organization of subcellular cargoes including organelles, vesicles, mRNA particles, and even viruses (Vale, 2003). Defects in intracellular transport have been linked to a range of diseases including neurodegeneration and cancer (Hirokawa et al., 2010; Yu and Feng, 2010). Although the biophysical and biochemical properties of individual motor proteins are well-characterized, the collective behavior of motors is less clear despite evidence that multiple motors are present on a given cellular cargo (eg, Miller and Lasek, 1985; Ashkin et al., 1990; Snow et al., 2004; Shubeita et al., 2008; Laib et al., 2009; Soppina et al., 2009; Hendricks et al., 2010, 2012). Detailed investigation of this collective behavior is crucial and necessary for understanding transport processes in the cell. Intuitively, multiple motors are expected to cooperate to generate longer transport distances and sufficient force to pull a bulky cargo through the crowded cytoplasm at efficient speeds. Previous work reconstituting motor–cargo interactions in vitro supported these ideas, showing enhanced run lengths and higher forces for multiple kinesin-1 motors on plastic beads or quantum dots (Block et al., 1990; Vershinin et al., 2007; Beeg et al., 2008; Conway et al., 2012). Theoretical studies using meanfield and Monte Carlo approaches represent ideal motor efficiency and generally agree with these in vitro studies (Klumpp and Lipowsky, 2005; Kunwar et al., 2008). In contrast, recent in vitro studies using precisely defined DNA-based motor assemblies show that the run length enhancements caused by multiple kinesin-1 motors are much smaller than what is predicted by theory, and assemblies of exactly two motors show only a modest run length increase (Rogers et al., 2009; Derr et al., 2012; Furuta et al., 2013). This result has been interpreted as negative interference between kinesin motors (Rogers et al., 2009) that can result in a decrease in motor velocity at very high motor concentrations (Bieling et al., 2008; Conway et al., 2012; Furuta et al., 2013). A load-dependent study of DNA-based motor assemblies showed that although two kinesin-1 motors are capable of generating additional force, they typically only used the action of one motor (Jamison et al., 2010). Thus, any cooperation between kinesin motors remains poorly understood.
