scholarly journals Spectrin is a mechanoresponsive protein shaping the architecture of intercellular invasion

2017 ◽  
Author(s):  
Rui Duan ◽  
Ji Hoon Kim ◽  
Khurts Shilagardi ◽  
Eric Schiffhauer ◽  
Sungmin Son ◽  
...  
Keyword(s):  
Cell Fusion ◽  
Cell Biology ◽  
Cell Shape ◽  
Myosin Ii ◽  
Mechanical Damage ◽  
Fusion Partner ◽  
Mechanical Tension ◽  
Cellular Processes ◽  
Skeletal Protein ◽  
Cell Cell

Spectrin is a membrane skeletal protein best known for its structural role in maintaining cell shape and protecting cells from mechanical damage1-3. Here, we report that spectrin dynamically accumulates and dissolves at the fusogenic synapse, where an attacking fusion partner mechanically invades its receiving partner with actin-propelled protrusions to promote cell-cell fusion4-7. Using genetics, cell biology, biophysics and mathematical modeling, we demonstrate that unlike myosin II that responds to dilation deformation, spectrin exhibits a mechanosensitive accumulation in response to shear deformation, which is highly elevated at the fusogenic synapse. The accumulated spectrin forms an uneven network, which functions as a “sieve” to constrict the invasive fingerlike protrusions, thus putting the fusogenic synapse under high mechanical tension to promote cell membrane fusion. Taken together, our study has revealed a previously unrecognized function of spectrin as a dynamic mechanoresponsive protein that shapes the architecture of intercellular invasion. These findings have general implications for understanding spectrin function in other dynamic cellular processes beyond cell-cell fusion.

scholarly journals Mechanical stress impairs pheromone signaling via Pkc1-mediated regulation of the MAPK scaffold Ste5

2019 ◽  
Vol 218 (9) ◽  
pp. 3117-3133 ◽  
Author(s):  
Frank van Drogen ◽  
Ranjan Mishra ◽  
Fabian Rudolf ◽  
Michal J. Walczak ◽  
Sung Sik Lee ◽  
...  
Keyword(s):  
Mechanical Stress ◽  
Cell Fusion ◽  
Polarized Growth ◽  
Conserved Residues ◽  
Cellular Processes ◽  
Pheromone Signaling ◽  
Stress Signals ◽  
Cell Cell

Cells continuously adapt cellular processes by integrating external and internal signals. In yeast, multiple stress signals regulate pheromone signaling to prevent mating under unfavorable conditions. However, the underlying crosstalk mechanisms remain poorly understood. Here, we show that mechanical stress activates Pkc1, which prevents lysis of pheromone-treated cells by inhibiting polarized growth. In vitro Pkc1 phosphorylates conserved residues within the RING-H2 domains of the scaffold proteins Far1 and Ste5, which are also phosphorylated in vivo. Interestingly, Pkc1 triggers dispersal of Ste5 from mating projections upon mechanically induced stress and during cell–cell fusion, leading to inhibition of the MAPK Fus3. Indeed, RING phosphorylation interferes with Ste5 membrane association by preventing binding to the receptor-linked Gβγ protein. Cells expressing nonphosphorylatable Ste5 undergo increased lysis upon mechanical stress and exhibit defects in cell–cell fusion during mating, which is exacerbated by simultaneous expression of nonphosphorylatable Far1. These results uncover a mechanical stress–triggered crosstalk mechanism modulating pheromone signaling, polarized growth, and cell–cell fusion during mating.

scholarly journals Let curiosity lead you

2018 ◽  
Vol 29 (22) ◽  
pp. 2603-2605
Author(s):  
Elizabeth H. Chen
Keyword(s):  
Cell Fusion ◽  
Cell Biology ◽  
Multicellular Organisms ◽  
To Receive ◽  
Cell Cell

It is an incredible honor to receive the Woman in Cell Biology Mid-Career Award for Excellence in Research. My lab works on cell–cell fusion, an indispensable process in the conception, development, and physiology of multicellular organisms. In this essay, I reflect on my curiosity-led journey, which uncovered some unexpected mechanisms underlying cell–cell fusion.

scholarly journals Myosin II Functions as a Direct Mechanosensor for Intercellular Invasion during Cell-Cell Fusion

2014 ◽  
Vol 106 (2) ◽  
pp. 574a
Author(s):  
Ji Hoon Kim ◽  
Yixin Ren ◽  
Shuo Li ◽  
Yee Kee ◽  
Guofeng Zhang ◽  
...  
Keyword(s):  
Cell Fusion ◽  
Myosin Ii ◽  
Cell Cell

scholarly journals The mechanobiology of actin cytoskeletal proteins during cell–cell fusion

2019 ◽  
Vol 16 (156) ◽  
pp. 20190022 ◽  
Author(s):  
Jing Cong ◽  
Bing Fang ◽  
Qian Wang ◽  
Yan Su ◽  
Tianqi Gu ◽  
...  
Keyword(s):  
Cell Fusion ◽  
Myosin Ii ◽  
Mean Field Theory ◽  
Mean Field ◽  
Local Area ◽  
Quantitative Model ◽  
Local Deformation ◽  
Cytoskeletal Proteins ◽  
Fusion Pore ◽  
Cell Cell

Myosin II and spectrin β display mechanosensitive accumulations in invasive protrusions during cell–cell fusion of Drosophila myoblasts. The biochemical inhibition and deactivation of these proteins results in significant fusion defects. Yet, a quantitative understanding of how the protrusion geometry and fusion process are linked to these proteins is still lacking. Here we present a quantitative model to interpret the dependence of the protrusion size and the protrusive force on the mechanical properties and microstructures of the actin cytoskeleton and plasma membrane based on a mean-field theory. We build a quantitative linkage between mechanosensitive accumulation of myosin II and fusion pore formation at the tip of the invasive protrusion through local area dilation. The mechanical feedback loop between myosin II and local deformation suggests that myosin II accumulation possibly reduces the energy barrier and the critical radius of fusion pores. We also analyse the effect of spectrin β on maintaining the proper geometry of the protrusions required for the success of cell–cell fusion.

scholarly journals Establishment of morphological atlas of Caenorhabditis elegans embryo with cellular resolution using deep-learning-based 4D segmentation

2019 ◽  
Author(s):  
Jianfeng Cao ◽  
Guoye Guan ◽  
Ming-Kin Wong ◽  
Lu-Yan Chan ◽  
Chao Tang ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cell Biology ◽  
Cell Shape ◽  
Shape Change ◽  
Shape Reconstruction ◽  
Cell Contact ◽  
Spatiotemporal Resolution ◽  
C Elegans ◽  
Cell Shape Change ◽  
Cell Cell

Cell lineage consists of cell division timing, cell migration and cell fate, which are highly reproducible during the development of some nematode species, including C. elegans. Due to the lack of high spatiotemporal resolution of imaging technique and reliable shape-reconstruction algorithm, cell morphology have not been systematically characterized in depth over development for any metazoan. This significantly inhibits the study of space-related problems in developmental biology, including cell segregation, cell-cell contact and cell shape change over development. Here we develop an automated pipeline, CShaper, to help address these issues. By quantifying morphological parameters of densely packed cells in developing C. elegans emrbyo through segmentation of fluorescene-labelled membrance, we generate a time-lapse framework of cellular shape and migration for C. elegans embryos from 4-to 350-cell stage, including a full migration trajectory, morphological dynamics of 226 cells and 877 reproducible cell-cell contacts. In combination with automated cell tracing, cell-fate associated cell shape change becomes within reach. Our work provides a quantitative resource for C. elegans early development, which is expected to facilitate the research such as signaling transduction and cell biology of division.

scholarly journals Lulu2 regulates the circumferential actomyosin tensile system in epithelial cells through p114RhoGEF

2011 ◽  
Vol 195 (2) ◽  
pp. 245-261 ◽  
Author(s):  
Hiroyuki Nakajima ◽  
Takuji Tanoue
Keyword(s):  
Epithelial Cells ◽  
Cell Shape ◽  
Molecular Mechanisms ◽  
Molecular System ◽  
Apical Cell ◽  
Cell Junctions ◽  
Cellular Processes ◽  
Kinase C ◽  
Important Regulator ◽  
Cell Cell

Myosin II–driven mechanical forces control epithelial cell shape and morphogenesis. In particular, the circumferential actomyosin belt, which is located along apical cell–cell junctions, regulates many cellular processes. Despite its importance, the molecular mechanisms regulating the belt are not fully understood. In this paper, we characterize Lulu2, a FERM (4.1 protein, ezrin, radixin, moesin) domain–containing molecule homologous to Drosophila melanogaster Yurt, as an important regulator. In epithelial cells, Lulu2 is localized along apical cell–cell boundaries, and Lulu2 depletion by ribonucleic acid interference results in disorganization of the circumferential actomyosin belt. In its regulation of the belt, Lulu2 interacts with and activates p114RhoGEF, a Rho-specific guanine nucleotide exchanging factor (GEF), at apical cell–cell junctions. This interaction is negatively regulated via phosphorylation events in the FERM-adjacent domain of Lulu2 catalyzed by atypical protein kinase C. We further found that Patj, an apical cell polarity regulator, recruits p114RhoGEF to apical cell–cell boundaries via PDZ (PSD-95/Dlg/ZO-1) domain–mediated interaction. These findings therefore reveal a novel molecular system regulating the circumferential actomyosin belt in epithelial cells.

scholarly journals Direct transfer of learned behaviour via cell fusion in non-neural organisms

2016 ◽  
Vol 283 (1845) ◽  
pp. 20162382 ◽  
Author(s):  
David Vogel ◽  
Audrey Dussutour
Keyword(s):  
Cell Fusion ◽  
Adaptive Response ◽  
Fusion Partner ◽  
Slime Mould ◽  
Behavioural Adaptation ◽  
Slime Moulds ◽  
A Cell ◽  
Fundamental Phenomenon ◽  
Effective Transfer ◽  
Cell Cell

Cell fusion is a fundamental phenomenon observed in all eukaryotes. Cells can exchange resources such as molecules or organelles during fusion. In this paper, we ask whether a cell can also transfer an adaptive response to a fusion partner. We addressed this question in the unicellular slime mould Physarum polycephalum , in which cell–cell fusion is extremely common. Slime moulds are capable of habituation, a simple form of learning, when repeatedly exposed to an innocuous repellent, despite lacking neurons and comprising only a single cell. In this paper, we present a set of experiments demonstrating that slime moulds habituated to a repellent can transfer this adaptive response by cell fusion to individuals that have never encountered the repellent. In addition, we show that a slime mould resulting from the fusion of a minority of habituated slime moulds and a majority of unhabituated ones still shows an adaptive response to the repellent. Finally, we further reveal that fusion must last a certain time to ensure an effective transfer of the behavioural adaptation between slime moulds. Our results provide strong experimental evidence that slime moulds exhibit transfer of learned behaviour during cell fusion and raise the possibility that similar phenomena may occur in other cell–cell fusion systems.

scholarly journals High-Temperature Live-Cell Imaging of Cytokinesis, Cell Motility, and Cell-Cell Interactions in the Thermoacidophilic Crenarchaeon Sulfolobus acidocaldarius

2021 ◽  
Vol 12 ◽  
Author(s):  
Arthur Charles-Orszag ◽  
Samuel J. Lord ◽  
R. Dyche Mullins
Keyword(s):  
High Temperature ◽  
Cell Motility ◽  
Cell Biology ◽  
Cell Shape ◽  
Numerical Aperture ◽  
Cell Interactions ◽  
Sulfolobus Acidocaldarius ◽  
Dynamic Cell ◽  
Shape Changes ◽  
Cell Cell

Significant technical challenges have limited the study of extremophile cell biology. Here we describe a system for imaging samples at 75°C using high numerical aperture, oil-immersion lenses. With this system we observed and quantified the dynamics of cell division in the model thermoacidophilic crenarchaeon Sulfolobus acidocaldarius with unprecedented resolution. In addition, we observed previously undescribed dynamic cell shape changes, cell motility, and cell-cell interactions, shedding significant new light on the high-temperature lifestyle of this organism.

scholarly journals Forces that shape fission yeast cells

2017 ◽  
Vol 28 (14) ◽  
pp. 1819-1824 ◽  
Author(s):  
Fred Chang
Keyword(s):  
Fission Yeast ◽  
Cell Biology ◽  
Cell Shape ◽  
Turgor Pressure ◽  
Cell Types ◽  
Yeast Cells ◽  
Animal Cells ◽  
Cellular Mechanics ◽  
Cellular Processes ◽  
Micrometer Scale

One of the major challenges of modern cell biology is to understand how cells are assembled from nanoscale components into micrometer-scale entities with a specific size and shape. Here I describe how our quest to understand the morphogenesis of the fission yeast Schizosaccharomyces pombe drove us to investigate cellular mechanics. These studies build on the view that cell shape arises from the physical properties of an elastic cell wall inflated by internal turgor pressure. Consideration of cellular mechanics provides new insights into not only mechanisms responsible for cell-shape determination and growth, but also cellular processes such as cytokinesis and endocytosis. Studies in yeast can help to illuminate approaches and mechanisms to study the mechanobiology of the cell surface in other cell types, including animal cells.

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