scholarly journals On the Role of Curved Membrane Nanodomains and Passive and Active Skeleton Forces in the Determination of Cell Shape and Membrane Budding

2021 ◽  
Vol 22 (5) ◽  
pp. 2348
Author(s):  
Luka Mesarec ◽  
Mitja Drab ◽  
Samo Penič ◽  
Veronika Kralj-Iglič ◽  
Aleš Iglič
Keyword(s):  
Actin Cytoskeleton ◽  
Cell Shape ◽  
Critical Concentration ◽  
Equilibrium Shape ◽  
Orientation Angle ◽  
Membrane Skeleton ◽  
Membrane Protrusions ◽  
Membrane Budding ◽  
Curved Membrane

Biological membranes are composed of isotropic and anisotropic curved nanodomains. Anisotropic membrane components, such as Bin/Amphiphysin/Rvs (BAR) superfamily protein domains, could trigger/facilitate the growth of membrane tubular protrusions, while isotropic curved nanodomains may induce undulated (necklace-like) membrane protrusions. We review the role of isotropic and anisotropic membrane nanodomains in stability of tubular and undulated membrane structures generated or stabilized by cyto- or membrane-skeleton. We also describe the theory of spontaneous self-assembly of isotropic curved membrane nanodomains and derive the critical concentration above which the spontaneous necklace-like membrane protrusion growth is favorable. We show that the actin cytoskeleton growth inside the vesicle or cell can change its equilibrium shape, induce higher degree of segregation of membrane nanodomains or even alter the average orientation angle of anisotropic nanodomains such as BAR domains. These effects may indicate whether the actin cytoskeleton role is only to stabilize membrane protrusions or to generate them by stretching the vesicle membrane. Furthermore, we demonstrate that by taking into account the in-plane orientational ordering of anisotropic membrane nanodomains, direct interactions between them and the extrinsic (deviatoric) curvature elasticity, it is possible to explain the experimentally observed stability of oblate (discocyte) shapes of red blood cells in a broad interval of cell reduced volume. Finally, we present results of numerical calculations and Monte-Carlo simulations which indicate that the active forces of membrane skeleton and cytoskeleton applied to plasma membrane may considerably influence cell shape and membrane budding.

scholarly journals PFN2 and NAA80 cooperate to efficiently acetylate the N-terminus of actin

2020 ◽  
Author(s):  
Rasmus Ree ◽  
Laura Kind ◽  
Anna Kaziales ◽  
Sylvia Varland ◽  
Minglu Dai ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Actin Cytoskeleton ◽  
Actin Filament ◽  
Cell Shape ◽  
Specific Role ◽  
Force Generation ◽  
Filament Formation ◽  
Modus Operandi ◽  
N Terminus

AbstractThe actin cytoskeleton is of profound importance to cell shape, division, and intracellular force generation. Profilins bind to globular (G-)actin and regulate actin filament formation. Although profilins are well-established actin regulators, the distinct roles of the dominant profilin, profilin 1 (PFN1), versus the less abundant profilin 2 (PFN2) remain enigmatic. Here, we define a specific role for PFN2 as a stable interactor and regulator of the actin N-terminal acetyltransferase NAA80. PFN2 binding increases the intrinsic catalytic activity of NAA80. Furthermore, binding of PFN2 to NAA80 via its proline-rich loop promotes binding between the globular domains of actin and NAA80, and thus acetylation of actin. The majority of NAA80 is stably bound to PFN2, and we propose that this complex acetylates G-actin before it is incorporated into filaments. In conclusion, we reveal a functionally specific role of PFN2, and establish the modus operandi for NAA80-mediated actin N-terminal acetylation. Data are available via ProteomeXchange with identifier PXD020188.

scholarly journals Apical Spectrin Is Essential for Epithelial Morphogenesis but Not Apicobasal Polarity in Drosophila

1999 ◽  
Vol 146 (5) ◽  
pp. 1075-1086 ◽  
Author(s):  
Daniela C. Zarnescu ◽  
Graham H. Thomas
Keyword(s):  
Cell Shape ◽  
Follicle Cell ◽  
Membrane Skeleton ◽  
Epithelial Morphogenesis ◽  
Follicle Cells ◽  
Direct Role ◽  
Apical Constriction ◽  
Border Cell ◽  
Apicobasal Polarity

Changes in cell shape and position drive morphogenesis in epithelia and depend on the polarized nature of its constituent cells. The spectrin-based membrane skeleton is thought to be a key player in the establishment and/or maintenance of cell shape and polarity. We report that apical βHeavy-spectrin (βH), a terminal web protein that is also associated with the zonula adherens, is essential for normal epithelial morphogenesis of the Drosophila follicle cell epithelium during oogenesis. Elimination of βH by the karst mutation prevents apical constriction of the follicle cells during mid-oogenesis, and is accompanied by a gross breakup of the zonula adherens. We also report that the integrity of the migratory border cell cluster, a group of anterior follicle cells that delaminates from the follicle epithelium, is disrupted. Elimination of βH prevents the stable recruitment of α-spectrin to the apical domain, but does not result in a loss of apicobasal polarity, as would be predicted from current models describing the role of spectrin in the establishment of cell polarity. These results demonstrate a direct role for apical (αβH)2-spectrin in epithelial morphogenesis driven by apical contraction, and suggest that apical and basolateral spectrin do not play identical roles in the generation of apicobasal polarity.

scholarly journals Bursa-Derived Cells Show a Distinct Mechano-Response to Physiological and Pathological Loading in vitro

2021 ◽  
Vol 9 ◽  
Author(s):  
Franka Klatte-Schulz ◽  
Nicole Bormann ◽  
Isabel Voss ◽  
Josephine Melzer ◽  
Aysha Schmock ◽  
...  
Keyword(s):  
Gene Expression ◽  
Actin Cytoskeleton ◽  
Cell Viability ◽  
Mechanical Loading ◽  
Nuclear Translocation ◽  
Orientation Angle ◽  
Physiological Role ◽  
Type I ◽  
Subacromial Bursa

The mechano-response of highly loaded tissues such as bones or tendons is well investigated, but knowledge regarding the mechano-responsiveness of adjacent tissues such as the subacromial bursa is missing. For a better understanding of the physiological role of the bursa as a friction-reducing structure in the joint, the study aimed to analyze whether and how bursa-derived cells respond to physiological and pathological mechanical loading. This might help to overcome some of the controversies in the field regarding the role of the bursa in the development and healing of shoulder pathologies. Cells of six donors seeded on collagen-coated silicon dishes were stimulated over 3 days for 1 or 4 h with 1, 5, or 10% strain. Orientation of the actin cytoskeleton, YAP nuclear translocation, and activation of non-muscle myosin II (NMM-II) were evaluated for 4 h stimulations to get a deeper insight into mechano-transduction processes. To investigate the potential of bursa-derived cells to adapt their matrix formation and remodeling according to mechanical loading, outcome measures included cell viability, gene expression of extracellular matrix and remodeling markers, and protein secretions. The orientation angle of the actin cytoskeleton increased toward a more perpendicular direction with increased loading and lowest variations for the 5% loading group. With 10% tension load, cells were visibly stressed, indicated by loss in actin density and slightly reduced cell viability. A significantly increased YAP nuclear translocation occurred for the 1% loading group with a similar trend for the 5% group. NMM-II activation was weak for all stimulation conditions. On the gene expression level, only the expression of TIMP2 was down-regulated in the 1 h group compared to control. On the protein level, collagen type I and MMP2 increased with higher/longer straining, respectively, whereas TIMP1 secretion was reduced, resulting in an MMP/TIMP imbalance. In conclusion, this study documents for the first time a clear mechano-responsiveness in bursa-derived cells with activation of mechano-transduction pathways and thus hint to a physiological function of mechanical loading in bursa-derived cells. This study represents the basis for further investigations, which might lead to improved treatment options of subacromial bursa-related pathologies in the future.

scholarly journals Red blood cell shape and deformability in the context of the functional evolution of its membrane structure

2012 ◽  
Vol 17 (2) ◽  
Author(s):  
Saša Svetina
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Cell Shape ◽  
Transmembrane Protein ◽  
Membrane Skeleton ◽  
Bilayer Membrane ◽  
Membrane Area ◽  
Membrane Interaction ◽  
Protein Membrane

AbstractIt is proposed that it is possible to identify some of the problems that had to be solved in the course of evolution for the red blood cell (RBC) to achieve its present day effectiveness, by studying the behavior of systems featuring different, partial characteristics of its membrane. The appropriateness of the RBC volume to membrane area ratio for its circulation in the blood is interpreted on the basis of an analysis of the shape behavior of phospholipid vesicles. The role of the membrane skeleton is associated with preventing an RBC from transforming into a budded shape, which could form in its absence due to curvature-dependent transmembrane protein-membrane interaction. It is shown that, by causing the formation of echinocytes, the skeleton also acts protectively when, in vesicles with a bilayer membrane, the budded shapes would form due to increasing difference between the areas of their outer and inner layers.

scholarly journals EpCAM promotes endosomal modulation of the cortical RhoA zone for epithelial organization

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Cécile Gaston ◽  
Simon De Beco ◽  
Bryant Doss ◽  
Meng Pan ◽  
Estelle Gauquelin ◽  
...  
Keyword(s):  
Cell Shape ◽  
Specific Protein ◽  
Cell Polarization ◽  
Stress Fiber ◽  
Fiber Formation ◽  
Endosomal Trafficking ◽  
Transient Zone ◽  
And Behavior ◽  
Fine Tune

AbstractAt the basis of cell shape and behavior, the organization of actomyosin and its ability to generate forces are widely studied. However, the precise regulation of this contractile network in space and time is unclear. Here, we study the role of the epithelial-specific protein EpCAM, a contractility modulator, in cell shape and motility. We show that EpCAM is required for stress fiber generation and front-rear polarity acquisition at the single cell level. In fact, EpCAM participates in the remodeling of a transient zone of active RhoA at the cortex of spreading epithelial cells. EpCAM and RhoA route together through the Rab35/EHD1 fast recycling pathway. This endosomal pathway spatially organizes GTP-RhoA to fine tune the activity of actomyosin resulting in polarized cell shape and development of intracellular stiffness and traction forces. Impairment of GTP-RhoA endosomal trafficking either by silencing EpCAM or by expressing Rab35/EHD1 mutants prevents proper myosin-II activity, stress fiber formation and ultimately cell polarization. Collectively, this work shows that the coupling between co-trafficking of EpCAM and RhoA, and actomyosin rearrangement is pivotal for cell spreading, and advances our understanding of how biochemical and mechanical properties promote cell plasticity.

Membrane Homeostasis: The Role of Actin Cytoskeleton

2021 ◽  
Vol 101 (1) ◽  
pp. 81-95
Author(s):  
Arikta Biswas ◽  
Rinku Kumar ◽  
Bidisha Sinha
Keyword(s):  
Actin Cytoskeleton

EB1 Is Essential for Spindle Formation and Chromosome Alignment During Oocyte Meiotic Maturation in Mice

2021 ◽  
pp. 1-7
Author(s):  
Dongjie Zhou ◽  
Zheng-Wen Nie ◽  
Xiang-Shun Cui
Keyword(s):  
Cell Shape ◽  
Control Cell ◽  
Meiotic Maturation ◽  
Junctional Complex ◽  
Spindle Formation ◽  
Oocyte Meiosis ◽  
Polarized Cell Growth ◽  
Chromosome Alignment ◽  
Oocyte Meiotic Maturation

The cytoskeleton plays an orchestrating role in polarized cell growth. Microtubules (MTs) not only play critical roles in chromosome alignment and segregation but also control cell shape, division, and motility. A member of the plus-end tracking proteins, end-binding protein 1 (EB1), regulates MT dynamics and plays vital roles in maintaining spindle symmetry and chromosome alignment during mitosis. However, the role of EB1 in mouse oocyte meiosis remains unknown. Here, we examined the localization patterns and expression levels of EB1 at different stages. EB1 protein level was found to be stable during meiosis. EB1 mainly localized along the spindle and had a similar localization pattern as that of α-tubulin. The EB1 protein was degraded with a Trim-Away method, and the results were further confirmed with western blotting and immunofluorescence. At 12 h of culture after EB1 knockdown (KD), a reduced number of mature MII oocytes were observed. EB1 KD led to spindle disorganization, chromosome misalignment, and missegregation; β-catenin protein binds to actin via the adherens junctional complex, which was significantly reduced in the EB1 KD oocytes. Collectively, we propose that the impairment of EB1 function manipulates spindle formation, thereby promoting chromosomal loss, which is expected to fuel aneuploidy and possibly fertilization failure.

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