scholarly journals A mechanosensory system governs myosin II accumulation in dividing cells

2012 ◽  
Vol 23 (8) ◽  
pp. 1510-1523 ◽  
Author(s):  
Yee-Seir Kee ◽  
Yixin Ren ◽  
Danielle Dorfman ◽  
Miho Iijima ◽  
Richard Firtel ◽  
...  
Keyword(s):  
Mechanical Stress ◽  
Mitotic Spindle ◽  
Asymmetric Cell Division ◽  
Myosin Ii ◽  
Feedback Loops ◽  
Cleavage Furrow ◽  
Dividing Cells ◽  
Centromeric Protein ◽  
Protein Recruitment ◽  
Mechanosensory System

The mitotic spindle is generally considered the initiator of furrow ingression. However, recent studies suggest that furrows can form without spindles, particularly during asymmetric cell division. In Dictyostelium, the mechanoenzyme myosin II and the actin cross-linker cortexillin I form a mechanosensor that responds to mechanical stress, which could account for spindle-independent contractile protein recruitment. Here we show that the regulatory and contractility network composed of myosin II, cortexillin I, IQGAP2, kinesin-6 (kif12), and inner centromeric protein (INCENP) is a mechanical stress–responsive system. Myosin II and cortexillin I form the core mechanosensor, and mechanotransduction is mediated by IQGAP2 to kif12 and INCENP. In addition, IQGAP2 is antagonized by IQGAP1 to modulate the mechanoresponsiveness of the system, suggesting a possible mechanism for discriminating between mechanical and biochemical inputs. Furthermore, IQGAP2 is important for maintaining spindle morphology and kif12 and myosin II cleavage furrow recruitment. Cortexillin II is not directly involved in myosin II mechanosensitive accumulation, but without cortexillin I, cortexillin II's role in membrane–cortex attachment is revealed. Finally, the mitotic spindle is dispensable for the system. Overall, this mechanosensory system is structured like a control system characterized by mechanochemical feedback loops that regulate myosin II localization at sites of mechanical stress and the cleavage furrow.

scholarly journals A Mechanosensory System Governs Myosin II Cleavage Furrow Accumulation

2012 ◽  
Vol 102 (3) ◽  
pp. 349a
Author(s):  
Yee Seir Kee ◽  
Yixin Ren ◽  
Danielle Dorfman ◽  
Miho Iijima ◽  
Richard Firtel ◽  
...  
Keyword(s):  
Myosin Ii ◽  
Cleavage Furrow ◽  
Mechanosensory System

scholarly journals Specific polar subpopulations of astral microtubules control spindle orientation and symmetric neural stem cell division

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Felipe Mora-Bermúdez ◽  
Fumio Matsuzaki ◽  
Wieland B Huttner
Keyword(s):  
Cell Division ◽  
Basal Cell ◽  
Mitotic Spindle ◽  
Asymmetric Cell Division ◽  
Spindle Cell ◽  
Spindle Orientation ◽  
Cell Cortex ◽  
Dividing Cells ◽  
Stem Cell Division

Mitotic spindle orientation is crucial for symmetric vs asymmetric cell division and depends on astral microtubules. Here, we show that distinct subpopulations of astral microtubules exist, which have differential functions in regulating spindle orientation and division symmetry. Specifically, in polarized stem cells of developing mouse neocortex, astral microtubules reaching the apical and basal cell cortex, but not those reaching the central cell cortex, are more abundant in symmetrically than asymmetrically dividing cells and reduce spindle orientation variability. This promotes symmetric divisions by maintaining an apico-basal cleavage plane. The greater abundance of apical/basal astrals depends on a higher concentration, at the basal cell cortex, of LGN, a known spindle-cell cortex linker. Furthermore, newly developed specific microtubule perturbations that selectively decrease apical/basal astrals recapitulate the symmetric-to-asymmetric division switch and suffice to increase neurogenesis in vivo. Thus, our study identifies a novel link between cell polarity, astral microtubules, and spindle orientation in morphogenesis.

Myosin II-independent F-actin flow contributes to cell locomotion in dictyostelium

1999 ◽  
Vol 112 (6) ◽  
pp. 877-886 ◽  
Author(s):  
Y. Fukui ◽  
T. Kitanishi-Yumura ◽  
S. Yumura
Keyword(s):  
Cell Body ◽  
Myosin Ii ◽  
Cleavage Furrow ◽  
Organizational Changes ◽  
Cortical Actin ◽  
Charge Coupled Device ◽  
Cell Locomotion ◽  
Intensity Changes ◽  
Dividing Cells ◽  
Temporal And Spatial

While the treadmilling and retrograde flow of F-actin are believed to be responsible for the protrusion of leading edges, little is known about the mechanism that brings the posterior cell body forward. To elucidate the mechanism for global cell locomotion, we examined the organizational changes of filamentous (F-) actin in live Dictyostelium discoideum. We labeled F-actin with a trace amount of fluorescent phalloidin and analyzed its dynamics in nearly two-dimensional cells by using a sensitive, high-resolution charge-coupled device. We optically resolved a cyclic mode of tightening and loosening of fibrous cortical F-actin and quantitated its flow by measuring temporal and spatial intensity changes. The rate of F-actin flow was evaluated with respect to migration velocity and morphometric changes. In migrating monopodial cells, the cortical F-actin encircling the posterior cell body gradually accumulated into the tail end at a speed of 0.35 microm/minute. We show qualitatively and quantitatively that the F-actin flow is closely associated with cell migration. Similarly, in dividing cells, the cortical F-actin accumulated into the cleavage furrow. Although five times slower than the wild type, the F-actin also flows rearward in migrating mhcA- cells demonstrating that myosin II (‘conventional’ myosin) is not absolutely required for the observed dynamics of F-actin. Yet consistent with the reported transportation of ConA-beads, the direction of observed F-actin flow in Dictyostelium is conceptually opposite from a barbed-end binding to the plasma membrane. This study suggests that the posterior end of the cell has a unique motif that tugs the cortical actin layer rearward by means of a mechanism independent from myosin II; this mechanism may be also involved in cleavage furrow formation.

scholarly journals Novel Myosin Heavy Chain Kinase Involved in Disassembly of Myosin II Filaments and Efficient Cleavage in MitoticDictyostelium Cells

2002 ◽  
Vol 13 (12) ◽  
pp. 4333-4342 ◽  
Author(s):  
Akira Nagasaki ◽  
Go Itoh ◽  
Shigehiko Yumura ◽  
Taro Q.P. Uyeda
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Myosin Ii ◽  
Kinase Domain ◽  
Cleavage Furrow ◽  
Wild Type ◽  
Daughter Cells ◽  
Cleavage Process ◽  
Interphase Cells ◽  
Myosin Heavy Chain Kinase

We have cloned a full-length cDNA encoding a novel myosin II heavy chain kinase (mhckC) from Dictyostelium. Like other members of the myosin heavy chain kinase family, themhckC gene product, MHCK C, has a kinase domain in its N-terminal half and six WD repeats in the C-terminal half. GFP-MHCK C fusion protein localized to the cortex of interphase cells, to the cleavage furrow of mitotic cells, and to the posterior of migrating cells. These distributions of GFP-MHCK C always corresponded with that of myosin II filaments and were not observed in myosin II-null cells, where GFP-MHCK C was diffusely distributed in the cytoplasm. Thus, localization of MHCK C seems to be myosin II-dependent. Cells lacking the mhckC gene exhibited excessive aggregation of myosin II filaments in the cleavage furrows and in the posteriors of the daughter cells once cleavage was complete. The cleavage process of these cells took longer than that of wild-type cells. Taken together, these findings suggest MHCK C drives the disassembly of myosin II filaments for efficient cytokinesis and recycling of myosin II that occurs during cytokinesis.

glsA, a Volvox gene required for asymmetric division and germ cell specification, encodes a chaperone-like protein

Development ◽  
1999 ◽  
Vol 126 (4) ◽  
pp. 649-658 ◽  
Author(s):  
S.M. Miller ◽  
D.L. Kirk
Keyword(s):  
Mitotic Spindle ◽  
Site Directed Mutagenesis ◽  
Cell Specification ◽  
Division Plane ◽  
Binding Domains ◽  
Acid Protein ◽  
Germ Cell Specification ◽  
Asymmetric Divisions ◽  
Dividing Cells ◽  
Amino Acid Protein

The gls genes of Volvox are required for the asymmetric divisions that set apart cells of the germ and somatic lineages during embryogenesis. Here we used transposon tagging to clone glsA, and then showed that it is expressed maximally in asymmetrically dividing embryos, and that it encodes a 748-amino acid protein with two potential protein-binding domains. Site-directed mutagenesis of one of these, the J domain (by which Hsp40-class chaperones bind to and activate specific Hsp70 partners) abolishes the capacity of glsA to rescue mutants. Based on this and other considerations, including the fact that the GlsA protein is associated with the mitotic spindle, we discuss how it might function, in conjunction with an Hsp70-type partner, to shift the division plane in asymmetrically dividing cells.

scholarly journals Delay of HeLa cell cleavage into interphase using dihydrocytochalasin B: retention of a postmitotic spindle and telophase disc correlates with synchronous cleavage recovery.

1995 ◽  
Vol 131 (1) ◽  
pp. 191-205 ◽  
Author(s):  
S N Martineau ◽  
P R Andreassen ◽  
R L Margolis
Keyword(s):  
Mammalian Cell ◽  
Mitotic Spindle ◽  
Cyclin B ◽  
Cell Cortex ◽  
Cleavage Furrow ◽  
Actin Assembly ◽  
Cell Cleavage ◽  
Integral Structure ◽  
G1 Cells ◽  
Molecular Signals

The molecular signals that determine the position and timing of the cleavage furrow during mammalian cell cytokinesis are presently unknown. We have studied in detail the effect of dihydrocytochalasin B (DCB), a drug that interferes with actin assembly, on specific late mitotic events in synchronous HeLa cells. When cleavage furrow formation is blocked at 10 microM DCB, cells return to interphase by the criteria of reformation of nuclei with lamin borders, degradation of the cyclin B component of p34cdc2 kinase, and loss of mitosis specific MPM-2 antigens. However, the machinery for cell cleavage is retained for up to one hour into G1 when cleavage cannot proceed. The components retained consist prominently of a "postmitotic" spindle and a telophase disc, a structure templated by the mitotic spindle in anaphase that may determine the position and timing of the cleavage furrow. Upon release from DCB block, G1 cells proceed through a rapid and synchronous cleavage. We conclude that the mitotic spindle is not inevitably destroyed at the end of mitosis, but persists as an integral structure with the telophase disc in the absence of cleavage. We also conclude that cell cleavage can occur in G1, and is therefore an event metabolically independent of mitosis. The retained telophase disc may indeed signal the position of furrow formation, as G1 cleavage occurs only in the position where the retained disc underlies the cell cortex. The protocol we describe should now enable development of a model system for the study of mammalian cell cleavage as a synchronous event independent of mitosis.

scholarly journals Asymmetric cell division-dominant neutral drift model for normal intestinal stem cell homeostasis

2019 ◽  
Vol 316 (1) ◽  
pp. G64-G74 ◽  
Author(s):  
Yoshitatsu Sei ◽  
Jianying Feng ◽  
Carson C. Chow ◽  
Stephen A. Wank
Keyword(s):  
Cell Division ◽  
Mitotic Spindle ◽  
Asymmetric Cell Division ◽  
Dominant Mode ◽  
Lineage Tracing ◽  
Intestinal Stem Cells ◽  
In Vivo Studies ◽  
Neutral Drift ◽  
Drift Model

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.

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