scholarly journals A Scribble-E-cadherin complex controls daughter cell patterning by multiple mechanisms

2021 ◽  
Author(s):  
Anchi S Chann ◽  
Ye Chen ◽  
Tanja Kinwel ◽  
Patrick O Humbert ◽  
Sarah Russell
Keyword(s):  
Cell Division ◽  
Mitotic Spindle ◽  
Cell Patterning ◽  
Cell Junction ◽  
Multiple Cues ◽  
Daughter Cells ◽  
Control Orientation ◽  
Mcf10a Cells ◽  
And Control ◽  
E Cadherin

The fate of the two daughter cells is intimately connected to their positioning, which is in turn regulated by cell junction remodelling and orientation of the mitotic spindle. How multiple cues are integrated to dictate the ultimate patterning of daughters is not clear. Here, we identify novel mechanisms of regulation of daughter positioning in single MCF10A cells. The polarity protein, Scribble, links E-cadherin to NuMA and Arp2/3 signalling for sequential roles in daughter positioning. First Scribble transmits cues from E-cadherin localised in retraction fibres to control orientation of the mitotic spindle. Second, Scribble re-locates to the junction between the two daughters to allow a new E-cadherin-based-interface to form between them, influencing the width of the nascent daughter-daughter junction, generation of filopodia and subsequent cell patterning. Thus, E-cadherin and Scribble dynamically relocate to different intracellular sites during cell division to orient the mitotic spindle and control placement of the daughter cells after cell division.

scholarly journals Systems cell biology of the mitotic spindle

2010 ◽  
Vol 188 (1) ◽  
pp. 7-9
Author(s):  
Ramsey A. Saleem ◽  
John D. Aitchison
Keyword(s):  
Cell Division ◽  
Mitotic Spindle ◽  
Cell Biology ◽  
Systems Genetics ◽  
Mitotic Spindles ◽  
High Content Imaging ◽  
Controlled Assembly ◽  
Daughter Cells ◽  
And Function ◽  
Insight Into

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.

scholarly journals Combined effect of cell geometry and polarity domains determines the orientation of unequal division

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Benoit G Godard ◽  
Remi Dumollard ◽  
Carl-Philipp Heisenberg ◽  
Alex McDougall
Keyword(s):  
Cell Division ◽  
Mitotic Spindle ◽  
Cell Shape ◽  
Daughter Cell ◽  
Cleavage Plane ◽  
Mitotic Cell ◽  
Cell Geometry ◽  
Daughter Cells ◽  
Ascidian Embryos ◽  
Spindle Position

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).

scholarly journals Asymmetric cell division: microtubule dynamics and spindle asymmetry

2002 ◽  
Vol 115 (11) ◽  
pp. 2257-2264 ◽  
Author(s):  
Julia A. Kaltschmidt ◽  
Andrea H. Brand
Keyword(s):  
Cell Division ◽  
Cell Size ◽  
Mitotic Spindle ◽  
Asymmetric Cell Division ◽  
Model Organisms ◽  
Complex Nature ◽  
Daughter Cells ◽  
Cytoskeletal Dynamics ◽  
Insight Into

Asymmetric cell division can produce daughter cells with different developmental fates and is often accompanied by a difference in cell size. A number of recent genetic and in vivo imaging studies in Drosophilaand Caenorhabditis elegans have begun to elucidate the mechanisms underlying the rearrangements of the cytoskeleton that result in eccentrically positioned cleavage planes. As a result, we are starting to gain an insight into the complex nature of the signals controlling cytoskeletal dynamics in the dividing cell. In this commentary we discuss recent findings on how the mitotic spindle is positioned and on cleavage site induction and place them in the context of cell size asymmetry in different model organisms.

scholarly journals E-cadherin and LGN align epithelial cell divisions with tissue tension independently of cell shape

2017 ◽  
Vol 114 (29) ◽  
pp. E5845-E5853 ◽  
Author(s):  
Kevin C. Hart ◽  
Jiongyi Tan ◽  
Kathleen A. Siemers ◽  
Joo Yong Sim ◽  
Beth L. Pruitt ◽  
...  
Keyword(s):  
Cell Division ◽  
Cell Monolayer ◽  
Spindle Orientation ◽  
Tissue Cell ◽  
Cellular Behavior ◽  
Cell Monolayers ◽  
Daughter Cells ◽  
Cell Divisions ◽  
Tensile Forces ◽  
E Cadherin

Tissue morphogenesis requires the coordinated regulation of cellular behavior, which includes the orientation of cell division that defines the position of daughter cells in the tissue. Cell division orientation is instructed by biochemical and mechanical signals from the local tissue environment, but how those signals control mitotic spindle orientation is not fully understood. Here, we tested how mechanical tension across an epithelial monolayer is sensed to orient cell divisions. Tension across Madin–Darby canine kidney cell monolayers was increased by a low level of uniaxial stretch, which oriented cell divisions with the stretch axis irrespective of the orientation of the cell long axis. We demonstrate that stretch-induced division orientation required mechanotransduction through E-cadherin cell–cell adhesions. Increased tension on the E-cadherin complex promoted the junctional recruitment of the protein LGN, a core component of the spindle orientation machinery that binds the cytosolic tail of E-cadherin. Consequently, uniaxial stretch triggered a polarized cortical distribution of LGN. Selective disruption of trans engagement of E-cadherin in an otherwise cohesive cell monolayer, or loss of LGN expression, resulted in randomly oriented cell divisions in the presence of uniaxial stretch. Our findings indicate that E-cadherin plays a key role in sensing polarized tensile forces across the tissue and transducing this information to the spindle orientation machinery to align cell divisions.

scholarly journals Pericentromere tension is self-regulated by spindle structure in metaphase

2014 ◽  
Vol 205 (3) ◽  
pp. 313-324 ◽  
Author(s):  
Jeremy M. Chacón ◽  
Soumya Mukherjee ◽  
Breanna M. Schuster ◽  
Duncan J. Clarke ◽  
Melissa K. Gardner
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Division ◽  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Chromosome Structure ◽  
Wild Type ◽  
Checkpoint Signaling ◽  
Daughter Cells ◽  
Fluorescent Markers ◽  
Spindle Structure

During cell division, a mitotic spindle is built by the cell and acts to align and stretch duplicated sister chromosomes before their ultimate segregation into daughter cells. Stretching of the pericentromeric chromatin during metaphase is thought to generate a tension-based signal that promotes proper chromosome segregation. However, it is not known whether the mitotic spindle actively maintains a set point tension magnitude for properly attached sister chromosomes to facilitate robust mechanochemical checkpoint signaling. By imaging and tracking the thermal movements of pericentromeric fluorescent markers in Saccharomyces cerevisiae, we measured pericentromere stiffness and then used the stiffness measurements to quantitatively evaluate the tension generated by pericentromere stretch during metaphase in wild-type cells and in mutants with disrupted chromosome structure. We found that pericentromere tension in yeast is substantial (4–6 pN) and is tightly self-regulated by the mitotic spindle: through adjustments in spindle structure, the cell maintains wild-type tension magnitudes even when pericentromere stiffness is disrupted.

scholarly journals Helical Twist and Rotational Forces in the Mitotic Spindle

Biomolecules ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 132 ◽  
Author(s):  
Iva M. Tolić ◽  
Maja Novak ◽  
Nenad Pavin
Keyword(s):  
Cell Division ◽  
Mitotic Spindle ◽  
Three Dimensions ◽  
Experimental Techniques ◽  
Future Studies ◽  
Daughter Cells ◽  
Helical Twist ◽  
Complex Shapes ◽  
Sister Kinetochore ◽  
Tension And Compression

The mitotic spindle segregates chromosomes into two daughter cells during cell division. This process relies on the precise regulation of forces acting on chromosomes as the cell progresses through mitosis. The forces in the spindle are difficult to directly measure using the available experimental techniques. Here, we review the ideas and recent advances of how forces can be determined from the spindle shape. By using these approaches, it has been shown that tension and compression coexist along a single kinetochore fiber, which are balanced by a bridging fiber between sister kinetochore fibers. An extension of this approach to three dimensions revealed that microtubule bundles have rich shapes, and extend not simply like meridians on the Earth’s surface but, rather, twisted in a helical manner. Such complex shapes are due to rotational forces, which, in addition to linear forces, act in the spindle and may be generated by motor proteins such as kinesin-5. These findings open new questions for future studies, to understand the mechanisms of rotational forces and reveal their biological roles in cells.

scholarly journals Modelling chromosome dynamics in mitosis: a historical perspective on models of metaphase and anaphase in eukaryotic cells

2014 ◽  
Vol 4 (3) ◽  
pp. 20130073 ◽  
Author(s):  
Gul Civelekoglu-Scholey ◽  
Daniela Cimini
Keyword(s):  
Cell Division ◽  
Mitotic Spindle ◽  
Historical Perspective ◽  
Quantitative Modelling ◽  
Mitotic Apparatus ◽  
Form Of Life ◽  
Daughter Cells ◽  
The Past ◽  
Quantitative Understanding ◽  
Spindle Elongation

Mitosis is the process by which the genome is segregated to form two identical daughter cells during cell division. The process of cell division is essential to the maintenance of every form of life. However, a detailed quantitative understanding of mitosis has been difficult owing to the complexity of the process. Indeed, it has been long recognized that, because of the complexity of the molecules involved, their dynamics and their properties, the mitotic events that mediate the segregation of the genome into daughter nuclei cannot be fully understood without the contribution of mathematical/quantitative modelling. Here, we provide an overview of mitosis and describe the dynamic and mechanical properties of the mitotic apparatus. We then discuss several quantitative models that emerged in the past decades and made an impact on our understanding of specific aspects of mitosis, including the motility of the chromosomes within the mitotic spindle during metaphase and anaphase, the maintenance of spindle length during metaphase and the switch to spindle elongation that occurs during anaphase.

scholarly journals The mechanics of microtubule networks in cell division

2017 ◽  
Vol 216 (6) ◽  
pp. 1525-1531 ◽  
Author(s):  
Scott Forth ◽  
Tarun M. Kapoor
Keyword(s):  
Cell Division ◽  
Somatic Cell ◽  
Mitotic Spindle ◽  
Force Generation ◽  
Mechanical Forces ◽  
Daughter Cells ◽  
Self Organized ◽  
New Findings ◽  
Microtubule Networks ◽  
Spindle Function

The primary goal of a dividing somatic cell is to accurately and equally segregate its genome into two new daughter cells. In eukaryotes, this process is performed by a self-organized structure called the mitotic spindle. It has long been appreciated that mechanical forces must be applied to chromosomes. At the same time, the network of microtubules in the spindle must be able to apply and sustain large forces to maintain spindle integrity. Here we consider recent efforts to measure forces generated within microtubule networks by ensembles of key proteins. New findings, such as length-dependent force generation, protein clustering by asymmetric friction, and entropic expansion forces will help advance models of force generation needed for spindle function and maintaining integrity.

Centrosomes and mitotic spindle poles: a recent liaison?

2015 ◽  
Vol 43 (1) ◽  
pp. 13-18 ◽  
Author(s):  
Pavithra L. Chavali ◽  
Isabel Peset ◽  
Fanni Gergely
Keyword(s):  
Cell Division ◽  
Mitotic Spindle ◽  
Potential Benefit ◽  
Cell Types ◽  
Daughter Cells ◽  
Spindle Poles ◽  
Pericentriolar Material ◽  
Mitotic Spindle Assembly ◽  
Spindle Microtubules ◽  
Ordered Assembly

Centrosomes comprise two cylindrical centrioles embedded in the pericentriolar material (PCM). The PCM is an ordered assembly of large scaffolding molecules, providing an interaction platform for proteins involved in signalling, trafficking and most importantly microtubule nucleation and organization. In mitotic cells, centrosomes are located at the spindle poles, sites where spindle microtubules converge. However, certain cell types and organisms lack centrosomes, yet contain focused spindle poles, highlighting that despite their juxtaposition in cells, centrosomes and mitotic spindle poles are distinct physical entities. In the present paper, we discuss the origin of centrosomes and summarize their contribution to mitotic spindle assembly and cell division. We then describe the key molecular players that mediate centrosome attachment to mitotic spindle poles and explore why co-segregation of centrosomes and spindle poles into daughter cells is of potential benefit to organisms.

scholarly journals Activation of Discs large by aPKC aligns the mitotic spindle to the polarity axis during asymmetric cell division

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Ognjen Golub ◽  
Brett Wee ◽  
Rhonda A Newman ◽  
Nicole M Paterson ◽  
Kenneth E Prehoda
Keyword(s):  
Cell Division ◽  
Mitotic Spindle ◽  
Asymmetric Cell Division ◽  
Intramolecular Interaction ◽  
Spindle Orientation ◽  
Orientation Factor ◽  
Daughter Cells ◽  
Kinase C ◽  
Discs Large ◽  
Fate Determinants

Asymmetric division generates cellular diversity by producing daughter cells with different fates. In animals, the mitotic spindle aligns with Par complex polarized fate determinants, ensuring that fate determinant cortical domains are bisected by the cleavage furrow. Here, we investigate the mechanisms that couple spindle orientation to polarity during asymmetric cell division of Drosophila neuroblasts. We find that the tumor suppressor Discs large (Dlg) links the Par complex component atypical Protein Kinase C (aPKC) to the essential spindle orientation factor GukHolder (GukH). Dlg is autoinhibited by an intramolecular interaction between its SH3 and GK domains, preventing Dlg interaction with GukH at cortical sites lacking aPKC. When co-localized with aPKC, Dlg is phosphorylated in its SH3 domain which disrupts autoinhibition and allows GukH recruitment by the GK domain. Our work establishes a molecular connection between the polarity and spindle orientation machineries during asymmetric cell division.

Sign in / Sign up

Export Citation Format

Share Document