Astral microtubules control redistribution of dynein at the cell cortex to facilitate spindle positioning

Abstract

Cytoplasmic dynein is recruited to the cell cortex in early mitosis, where it can generate pulling forces on astral microtubules to position the mitotic spindle. Recent work has shown that dynein displays a dynamic asymmetric cortical localization, and that dynein recruitment is negatively regulated by spindle pole-proximity. This results in oscillating dynein recruitment to opposite sides of the cortex to center the mitotic spindle. However, although the centrosome-derived signal that promotes displacement of dynein has been identified, it is currently unknown how dynein is re-recruited to the cortex once it has been displaced. Here we show that re-recruitment of cortical dynein requires astral microtubules. We find that microtubules are necessary for the sustained localized enrichment of dynein at the cortex. Furthermore, we show that stabilization of astral microtubules causes spindle misorientation, followed by mispositioning of dynein at the cortex. Thus, our results demonstrate the importance of astral microtubules in the dynamic regulation of cortical dynein recruitment in mitosis.

Two populations of cytoplasmic dynein contribute to spindle positioning in C. elegans embryos

“…This strongly suggests that LIN-5 can recruit dynein directly from the cytoplasm as opposed to an MT-mediated delivery mechanism. MT-independent dynein recruitment has also been observed in nocodazole-treated mammalian cells; however, the correct cortical distribution of human dynein appears to depend on a dynamic astral MT network ( Tame et al, 2014 ). Similarly, the localization of cortical dynein seemed randomized after nocodazole treatment of C. elegans embryos.…”

Gamma-actin is involved in regulating centrosome function and mitotic progression in cancer cells

“…Reorganization of actin filaments to the cell cortex during mitosis is crucial for the interactions between the cell cortex and astral microtubules, which is thought to be important for spindle assembly and correct spindle orientation. 3,39 Disruption to the cortical actin perturbs the interaction of astral microtubules to the cortex and affects mitotic spindle orientation. 2,36 This redistribution of g-actin to the cell membrane observed in this study may interfere with astral microtubules tethering to the cell cortex.…”

The cytoskeleton in spermatogenesis

“…This type of mechanism is often employed to control cell distribution, and in this instance likely allows one daughter cell to remain attached to the basement membrane, self-renewing the SSC progenitor, while sending the more apical daughter into the differentiating pathway. Positioning of the spindle in this way is dependent on the interplay between astral spindle microtubules, the microtubuleassociated motor protein, dynein and the cell cortex (Lagos-Cabré & Moreno 2008, Mora-Bermúdez et al 2014, Tame et al 2014.…”