Faculty Opinions recommendation of Myosin-1C associates with microtubules and stabilizes the mitotic spindle during cell division.

Author(s):  
James Bamburg ◽  
O'Neil Wiggan
2019 ◽  
Vol 316 (1) ◽  
pp. G64-G74 ◽  
Author(s):  
Yoshitatsu Sei ◽  
Jianying Feng ◽  
Carson C. Chow ◽  
Stephen A. Wank

The normal intestinal epithelium is continuously regenerated at a rapid rate from actively cycling Lgr5-expressing intestinal stem cells (ISCs) that reside at the crypt base. Recent mathematical modeling based on several lineage-tracing studies in mice shows that the symmetric cell division-dominant neutral drift model fits well with the observed in vivo growth of ISC clones and suggests that symmetric divisions are central to ISC homeostasis. However, other studies suggest a critical role for asymmetric cell division in the maintenance of ISC homeostasis in vivo. Here, we show that the stochastic branching and Moran process models with both a symmetric and asymmetric division mode not only simulate the stochastic growth of the ISC clone in silico but also closely fit the in vivo stem cell dynamics observed in lineage-tracing studies. In addition, the proposed model with highest probability for asymmetric division is more consistent with in vivo observations reported here and by others. Our in vivo studies of mitotic spindle orientations and lineage-traced progeny pairs indicate that asymmetric cell division is a dominant mode used by ISCs under normal homeostasis. Therefore, we propose the asymmetric cell division-dominant neutral drift model for normal ISC homeostasis. NEW & NOTEWORTHY The prevailing mathematical model suggests that intestinal stem cells (ISCs) divide symmetrically. The present study provides evidence that asymmetric cell division is the major contributor to ISC maintenance and thus proposes an asymmetric cell division-dominant neutral drift model. Consistent with this model, in vivo studies of mitotic spindle orientation and lineage-traced progeny pairs indicate that asymmetric cell division is the dominant mode used by ISCs under normal homeostasis.


eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Thomas S McAlear ◽  
Susanne Bechstedt

Cells increase microtubule dynamics to make large rearrangements to their microtubule cytoskeleton during cell division. Changes in microtubule dynamics are essential for the formation and function of the mitotic spindle, and misregulation can lead to aneuploidy and cancer. Using in vitro reconstitution assays we show that the mitotic spindle protein Cytoskeleton-Associated Protein 2 (CKAP2) has a strong effect on nucleation of microtubules by lowering the critical tubulin concentration 100-fold. CKAP2 increases the apparent rate constant ka of microtubule growth by 50-fold and increases microtubule growth rates. In addition, CKAP2 strongly suppresses catastrophes. Our results identify CKAP2 as the most potent microtubule growth factor to date. These finding help explain CKAP2's role as an important spindle protein, proliferation marker, and oncogene.


2010 ◽  
Vol 188 (1) ◽  
pp. 7-9
Author(s):  
Ramsey A. Saleem ◽  
John D. Aitchison

Cell division depends critically on the temporally controlled assembly of mitotic spindles, which are responsible for the distribution of duplicated chromosomes to each of the two daughter cells. To gain insight into the process, Vizeacoumar et al., in this issue (Vizeacoumar et al. 2010. J. Cell Biol. doi:10.1083/jcb.200909013), have combined systems genetics with high-throughput and high-content imaging to comprehensively identify and classify novel components that contribute to the morphology and function of the mitotic spindle.


2010 ◽  
Vol 30 (14) ◽  
pp. 3519-3530 ◽  
Author(s):  
Geoffrey E. Woodard ◽  
Ning-Na Huang ◽  
Hyeseon Cho ◽  
Toru Miki ◽  
Gregory G. Tall ◽  
...  

ABSTRACT In model organisms, resistance to inhibitors of cholinesterase 8 (Ric-8), a G protein α (Gα) subunit guanine nucleotide exchange factor (GEF), functions to orient mitotic spindles during asymmetric cell divisions; however, whether Ric-8A has any role in mammalian cell division is unknown. We show here that Ric-8A and Gαi function to orient the metaphase mitotic spindle of mammalian adherent cells. During mitosis, Ric-8A localized at the cell cortex, spindle poles, centromeres, central spindle, and midbody. Pertussis toxin proved to be a useful tool in these studies since it blocked the binding of Ric-8A to Gαi, thus preventing its GEF activity for Gαi. Linking Ric-8A signaling to mammalian cell division, treatment of cells with pertussis toxin, reduction of Ric-8A expression, or decreased Gαi expression similarly affected metaphase cells. Each treatment impaired the localization of LGN (GSPM2), NuMA (microtubule binding nuclear mitotic apparatus protein), and dynein at the metaphase cell cortex and disturbed integrin-dependent mitotic spindle orientation. Live cell imaging of HeLa cells expressing green fluorescent protein-tubulin also revealed that reduced Ric-8A expression prolonged mitosis, caused occasional mitotic arrest, and decreased mitotic spindle movements. These data indicate that Ric-8A signaling leads to assembly of a cortical signaling complex that functions to orient the mitotic spindle.


1976 ◽  
Vol 54 (9) ◽  
pp. 995-1009 ◽  
Author(s):  
D. E. Harder

Before mitosis in intercellular Puccinia graminis f. sp. avenae, P. coronata f. sp. avenue, and axenic P. graminis f. sp. tritici and P. coronata, the nuclei were reduced in size by nucleolar extrusion and (or) partitioning of variable portions of the nucleus. Also there was increased vesiculation in the cytoplasm with a corresponding increase in lipid and carbohydrate storage material.The mitotic spindle first formed in one corner of the nucleus, then elongated until the spindle poles were oriented at either end of the nucleus. During the intermediate stages of mitosis the chromatin was arranged around the periphery of the spindle, which consisted mostly of chromosomal fibres. In the later stages the nucleus elongated and became dumbbell-shaped, with long straight fibres passing through the nucleus from pole to pole. The end of mitosis was marked by the chromatin assuming a ‘two-track’ configuration at the poles on either side of the intranuclear fibres and by the breakdown of the nuclear envelope in the constricted region of the dumbbell-shaped nucleus.After the daughter nuclei had separated, they migrated into new hyphal branches and septum synthesis was subsequently initiated. The septa grew by centripetal invagination in both the intercellular and the axenic hyphal states. There were often accumulations of mitochondria in the region of septal growth. Mature septa of intercellular P. coronata and axenic P. coronata and P. graminis tritici were typical of those found elsewhere in the rust fungi.


2003 ◽  
Vol 15 (1) ◽  
pp. 82-87 ◽  
Author(s):  
Hongyan Wang ◽  
Snezhana Oliferenko ◽  
Mohan K Balasubramanian

2009 ◽  
Vol 96 (3) ◽  
pp. 195a-196a
Author(s):  
Andrea Jiménez-Dalmaroni ◽  
Manuel Théry ◽  
Victor Racine ◽  
Michel Bornens ◽  
Frank Jülicher

2019 ◽  
Author(s):  
Hui-Shun Kuan ◽  
Meredith D. Betterton

AbstractDuring cell division, microtubules in the mitotic spindle form antiparallel overlaps near the center of the spindle. Kinesin motor proteins alter microtubule polymerization dynamics to regulate the length of these overlaps to maintain spindle integrity. Length regulation of antiparallel overlaps has been reconstituted with purified microtubules, crosslinkers, and motors. Here we develop a theory of steady-state overlap length which depends on the filament plus-end motor concentration, determined by a balance between motor arrival (motor binding and stepping in the overlap) and motor departure (motor unbinding from filament tips during depolymerization) in the absence of motor-driven sliding. Assuming that motors processively depolymerize and exhibit altered binding kinetics near MT plus-ends improves the agreement between theory and experiment. Our theory explains the origin of the experimentally observed critical concentration, a minimum motor concentration to observe a steady-state overlap length.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Benoit G Godard ◽  
Remi Dumollard ◽  
Carl-Philipp Heisenberg ◽  
Alex McDougall

Cell division orientation is thought to result from a competition between cell geometry and polarity domains controlling the position of the mitotic spindle during mitosis. Depending on the level of cell shape anisotropy or the strength of the polarity domain, one dominates the other and determines the orientation of the spindle. Whether and how such competition is also at work to determine unequal cell division (UCD), producing daughter cells of different size, remains unclear. Here, we show that cell geometry and polarity domains cooperate, rather than compete, in positioning the cleavage plane during UCDs in early ascidian embryos. We found that the UCDs and their orientation at the ascidian third cleavage rely on the spindle tilting in an anisotropic cell shape, and cortical polarity domains exerting different effects on spindle astral microtubules. By systematically varying mitotic cell shape, we could modulate the effect of attractive and repulsive polarity domains and consequently generate predicted daughter cell size asymmetries and position. We therefore propose that the spindle position during UCD is set by the combined activities of cell geometry and polarity domains, where cell geometry modulates the effect of cortical polarity domain(s).


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