Active contraction of microtubule networks

Abstract

Many cellular processes are driven by cytoskeletal assemblies. It remains unclear how cytoskeletal filaments and motor proteins organize into cellular scale structures and how molecular properties of cytoskeletal components affect the large-scale behaviors of these systems. Here, we investigate the self-organization of stabilized microtubules in Xenopus oocyte extracts and find that they can form macroscopic networks that spontaneously contract. We propose that these contractions are driven by the clustering of microtubule minus ends by dynein. Based on this idea, we construct an active fluid theory of network contractions, which predicts a dependence of the timescale of contraction on initial network geometry, a development of density inhomogeneities during contraction, a constant final network density, and a strong influence of dynein inhibition on the rate of contraction, all in quantitative agreement with experiments. These results demonstrate that the motor-driven clustering of filament ends is a generic mechanism leading to contraction.DOI: http://dx.doi.org/10.7554/eLife.10837.001

NuMA Recruits Dynein Activity to Microtubule Minus-Ends at Mitosis

“…The clustering of parallel microtubules into poles presents a geometric problem when forces are indiscriminately applied all along microtubules: inversely oriented motors between parallel microtubules will oppose each other, resulting in gridlock, unless symmetry is broken by dynein enrichment at microtubule minus-ends (Hyman and Karsenti, 1996;McIntosh et al, 1969;Surrey et al, 2001). In computational models, localizing a minus-end-directed motor at microtubule ends permits microtubule clustering into asters or poles (Foster et al, 2015;Goshima et al, 2005;Nedelec and Surrey, 2001;Surrey et al, 2001) and the emergence of a robust steady-state spindle length (Burbank et al, 2007). More recently, experimental work has shown that dynein-dynactin and NuMA do indeed selectively localize to spindle minus-ends, with dynein pulling on them after kinetochore-fiber (k-fiber) ablation in mammalian spindles (Elting et al, 2014;Sikirzhytski et al, 2014).…”

Bridging length scales to measure polymer assembly

“…An intensity image revealed that asters and other large assemblies of microtubules form within minutes of Taxol addition (Figure 3A), as observed previously (Verde et al. , 1991; Foster et al. , 2015).…”

Automated Multi-Peak Tracking Kymography (AMTraK): A Tool to Quantify Sub-Cellular Dynamics with Sub-Pixel Accuracy

“…In recent experiments by Foster et al [39] they examined the spontaneous contraction dynamics of radial MT arrays or asters labeled with Alexa647-tagged tubulin, in Xenopus egg extracts. We have taken a time-series of such asters from published data (kindly shared by the author Peter J.…”

“… (A) A time-series of MT asters undergoing fusion (time-series taken from previous work by Foster et al [39]) was analyzed using AMTraK. The grey scale bar indicates normalized fluorescence intensity of Alexa-647 labeled tubulin.…”