The novel actin/focal adhesion-associated protein MISP is involved in mitotic spindle positioning in human cells

Maier, Bettina; Kirsch, Michael; Anderhub, Simon; Zentgraf, Hanswalter; Krämer, Alwin

doi:10.4161/cc.24602

Cited by 43 publications

(62 citation statements)

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Section: Beyond the Ternary Complexmentioning

confidence: 87%

“…An alternative hypothesis is that actin-associated proteins interact with the plus-end of astral microtubules and thus stabilize their interaction with the cell cortex [60]. Compatible with this view, depletion of the actin-associated protein MISP results in shorter astral microtubules and spindle positioning defects [61,62].The lipid composition of the plasma membrane also plays a role in proper spindle positioning, as exemplified by the analysis of the casein kinase 1 CSNK-1 in nematodes [63 ]. C. elegans embryos depleted of CSNK-1 exhibit excess cortical GPR-1/2 and LIN-5, as well as pulling forces.…”

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confidence: 88%

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Mechanisms of spindle positioning: cortical force generators in the limelight

Kotak

Gönczy

2013

Current Opinion in Cell Biology

156

138

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Correct positioning of the spindle governs placement of the cytokinesis furrow and thus plays a crucial role in the partitioning of fate determinants and the disposition of daughter cells in a tissue. Converging evidence indicates that spindle positioning is often dictated by interactions between the plus-end of astral microtubules that emanate from the spindle poles and an evolutionary conserved cortical machinery that serves to pull on them. At the heart of this machinery lies a ternary complex (LIN-5/GPR-1/2/Ga in Caenorhabditis elegans and NuMA/LGN/Gai in Homo sapiens) that promotes the presence of the motor protein dynein at the cell cortex. In this review, we discuss how the above components contribute to spindle positioning and how the underlying mechanisms are precisely regulated to ensure the proper execution of this crucial process in metazoan organisms IntroductionThe mitotic spindle is a diamond-shaped microtubulebased structure that faithfully segregates sister chromatids during cell division. Several types of microtubules emanate from the spindle poles, including astral microtubules that reach out to the actin rich cortex located beneath the plasma membrane ( Figure 1a). Pulling forces exerted on the plus-end of astral microtubules at the cell cortex are critical for accurately positioning the spindle with respect to cell-intrinsic or cell-extrinsic spatial cues. In turn, correct spindle positioning dictates placement of the cytokinesis furrow and is thus essential for determining the relative size and spatial disposition of the resulting daughter cells [2]. Accurate spindle positioning also ensures that cell fate determinants are appropriately segregated into daughter cells during development and in stem cell lineages [3].What features of the cell cortex allow interactions with astral microtubules to orchestrate spindle positioning? Specialized cortical sites are key. Their importance has been suggested for instance by elegant experiments in Chaetopterus oocytes, in which the meiotic spindle pulled away from its cortical attachment site using a micro-needle returns to that location once released (Figure 1b). Such experiments illustrate the existence of a mechanical link between the spindle and specialized cortical regions [4,5]. Laser microsurgery experiments in Fusarium solani or C. elegans suggested that this link corresponds to astral microtubules connecting the spindle poles with the cell cortex [6,7,8,9,10 ]. Although not the focus of this review, there are instances where pulling forces are exerted along the length of astral microtubules instead of at their plusend located at the cell cortex [11,12,13]. Work in several systems in recent years has increased our understanding of the basic principles governing spindle positioning and identified core molecular players and aspects of their mechanism of action. In this brief review, we will focus on cortically driven spindle positioning in one-cell C. elegans embryos and mammalian cells in culture. In doing so, we will discuss the nature of the t...

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Section: Beyond the Ternary Complexmentioning

confidence: 87%

mentioning

confidence: 88%

Mechanisms of spindle positioning: cortical force generators in the limelight

Kotak

Gönczy

2013

Current Opinion in Cell Biology

156

138

View full text Add to dashboard Cite

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“…It was proposed that the extracellular matrix controls actin structure and dynamics at the membrane, which, in turn, impacts on the orientation of the mitotic spindle 39 , 41 . Consistently, a number of factors that localize to and regulate cortical actin networks, such as MISP, 42 , 43 LIM kinase, 44 Cdc42, 45 and PI(3)K 46 are found to be required for regulated spindle orientation. Although a full picture has yet to emerge, these findings support the idea that a combination of cell-intrinsic and -extrinsic factors mediates spindle orientation in cultured mammalian cells.…”

Section: Introductionmentioning

confidence: 89%

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

et al. 2014

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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.

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“…What has been unclear so far is the force transmission mechanism linking extracellular space and astral microtubules. A new study by Maier et al identifies MISP (mitotic interactor and substrate of Plk1) as the missing link in this network of force-transmitting elements 5 (Fig. 1).…”

mentioning

confidence: 99%