scholarly journals Myosin-driven actin-microtubule networks exhibit self-organized contractile dynamics

2021 ◽  
Vol 7 (6) ◽  
pp. eabe4334 ◽  
Author(s):  
Gloria Lee ◽  
Gregor Leech ◽  
Michael J. Rust ◽  
Moumita Das ◽  
Ryan J. McGorty ◽  
...  
Keyword(s):  
Flexural Rigidity ◽  
Dynamic Network ◽  
Actin Networks ◽  
Cellular Processes ◽  
Self Organized ◽  
Cytoskeletal Dynamics ◽  
Network Composition ◽  
Ballistic Contraction ◽  
Microtubule Networks ◽  
Open Question

The cytoskeleton is a dynamic network of proteins, including actin, microtubules, and their associated motor proteins, that enables essential cellular processes such as motility, division, and growth. While actomyosin networks are extensively studied, how interactions between actin and microtubules, ubiquitous in the cytoskeleton, influence actomyosin activity remains an open question. Here, we create a network of co-entangled actin and microtubules driven by myosin II. We combine dynamic differential microscopy, particle image velocimetry, and particle tracking to show that both actin and microtubules undergo ballistic contraction with unexpectedly indistinguishable characteristics. This contractility is distinct from faster disordered motion and rupturing that active actin networks exhibit. Our results suggest that microtubules enable self-organized myosin-driven contraction by providing flexural rigidity and enhanced connectivity to actin networks. Beyond the immediate relevance to cytoskeletal dynamics, our results shed light on the design of active materials that can be precisely tuned by the network composition.

scholarly journals Myosin-driven actin-microtubule networks exhibit self-organized contractile dynamics

2020 ◽  
Author(s):  
Gloria Lee ◽  
Michael J. Rust ◽  
Moumita Das ◽  
Ryan J. McGorty ◽  
Jennifer L. Ross ◽  
...  
Keyword(s):  
Flexural Rigidity ◽  
Dynamic Network ◽  
Actin Networks ◽  
Cellular Processes ◽  
Self Organized ◽  
Image Velocimetry ◽  
Ballistic Contraction ◽  
Microtubule Networks ◽  
Open Question ◽  
Diverse Interactions

AbstractThe cytoskeleton is a dynamic network of proteins, including actin, microtubules, and myosin, that enables essential cellular processes such as motility, division, mechanosensing, and growth. While actomyosin networks are extensively studied, how interactions between actin and microtubules, ubiquitous in the cytoskeleton, influence actomyosin activity remains an open question. Here, we create a network of co-entangled actin and microtubules driven by myosin II. We combine dynamic differential microscopy, particle image velocimetry and particle-tracking to show that both actin and microtubules in the network undergo ballistic contraction with surprisingly indistinguishable characteristics. This controlled contractility is distinct from the faster turbulent motion and rupturing that active actin networks exhibit. Our results suggest that microtubules can enable self-organized myosin-driven contraction by providing flexural rigidity and enhanced connectivity to actin networks. These results provide important new insight into the diverse interactions cells can use to tune activity, and offer a powerful platform for designing multifunctional materials with well-regulated activity.

scholarly journals Regulation of Rho GTPases in the Vasculature by Cullin3-Based E3 Ligase Complexes

2021 ◽  
Vol 9 ◽  
Author(s):  
Fabienne Podieh ◽  
Peter L. Hordijk
Keyword(s):  
Rho Gtpases ◽  
Vascular Function ◽  
Rho Gtpase ◽  
Current Knowledge ◽  
E3 Ligase ◽  
Small Gtpases ◽  
E3 Ligases ◽  
Cellular Processes ◽  
Ubiquitin E3 Ligase ◽  
Cytoskeletal Dynamics

Cullin3-based ubiquitin E3 ligases induce ubiquitination of substrates leading to their proteasomal or lysosomal degradation. BTB proteins serve as adaptors by binding to Cullin3 and recruiting substrate proteins, which enables specific recognition of a broad spectrum of targets. Hence, Cullin3 and its adaptors are involved in myriad cellular processes and organ functions. Cullin3-based ubiquitin E3 ligase complexes target small GTPases of the Rho subfamily, which are key regulators of cytoskeletal dynamics and cell adhesion. In this mini review, we discuss recent insights in Cullin3-mediated regulation of Rho GTPases and their impact on cellular function and disease. Intriguingly, upstream regulators of Rho GTPases are targeted by Cullin3 complexes as well. Thus, Rho GTPase signaling is regulated by Cullin3 on multiple levels. In addition, we address current knowledge of Cullin3 in regulating vascular function, focusing on its prominent role in endothelial barrier function, angiogenesis and the regulation of blood pressure.

scholarly journals Intersectin-1 interacts with the golgin GCC88 to couple the actin network and Golgi architecture

2019 ◽  
Vol 30 (3) ◽  
pp. 370-386 ◽  
Author(s):  
Christian Makhoul ◽  
Prajakta Gosavi ◽  
Regina Duffield ◽  
Bronwen Delbridge ◽  
Nicholas A. Williamson ◽  
...  
Keyword(s):  
Dynamic Balance ◽  
Nucleotide Exchange ◽  
Actin Networks ◽  
Guanine Nucleotide Exchange ◽  
Membrane Flux ◽  
Nucleotide Exchange Factor ◽  
Golgi Ribbon ◽  
Microtubule Networks ◽  
Golgi Network ◽  
Membrane Tether

The maintenance of the Golgi ribbon relies on a dynamic balance between the actin and microtubule networks; however, the pathways controlling actin networks remain poorly defined. Previously, we showed that the trans-Golgi network (TGN) membrane tether/golgin, GCC88, modulates the Golgi ribbon architecture. Here, we show that dispersal of the Golgi ribbon by GCC88 is dependent on actin and the involvement of nonmuscle myosin IIA. We have identified the long isoform of intersectin-1 (ITSN-1), a guanine nucleotide exchange factor for Cdc42, as a novel Golgi component and an interaction partner of GCC88 responsible for mediating the actin-dependent dispersal of the Golgi ribbon. We show that perturbation of Golgi morphology by changes in membrane flux, mediated by silencing the retromer subunit Vps26, or in a model of neurodegeneration, induced by Tau overexpression, are also dependent on the ITSN-1-GCC88 interaction. Overall, our study reveals a role for a TGN golgin and ITSN-1 in linking to the actin cytoskeleton and regulating the balance between a compact Golgi ribbon and a dispersed Golgi, a pathway with relevance to pathophysiological conditions.

scholarly journals What Role Does CFTR Play in Development, Differentiation, Regeneration and Cancer?

2020 ◽  
Vol 21 (9) ◽  
pp. 3133 ◽  
Author(s):  
Margarida D. Amaral ◽  
Margarida C. Quaresma ◽  
Ines Pankonien
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Transmembrane Conductance Regulator ◽  
Foetal Development ◽  
Term Survival ◽  
Mesenchymal Transition ◽  
Cellular Processes ◽  
Underlying Mechanisms ◽  
Novel Therapeutic Strategies ◽  
Open Question

One of the key features associated with the substantial increase in life expectancy for individuals with CF is an elevated predisposition to cancer, firmly established by recent studies involving large cohorts. With the recent advances in cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies and the increased long-term survival rate of individuals with cystic fibrosis (CF), this is a novel challenge emerging at the forefront of this disease. However, the mechanisms linking dysfunctional CFTR to carcinogenesis have yet to be unravelled. Clues to this challenging open question emerge from key findings in an increasing number of studies showing that CFTR plays a role in fundamental cellular processes such as foetal development, epithelial differentiation/polarization, and regeneration, as well as in epithelial–mesenchymal transition (EMT). Here, we provide state-of-the-art descriptions on the moonlight roles of CFTR in these processes, highlighting how they can contribute to novel therapeutic strategies. However, such roles are still largely unknown, so we need rapid progress in the elucidation of the underlying mechanisms to find the answers and thus tailor the most appropriate therapeutic approaches.

BIOMIMETIC SYSTEMS SHED LIGHT ON ACTIN-BASED MOTILITY DOWN TO THE MOLECULAR SCALE

2009 ◽  
Vol 04 (01n02) ◽  
pp. 5-15 ◽  
Author(s):  
GUILLAUME ROMET-LEMONNE ◽  
EMMANUELE HELFER ◽  
VINCENT DELATOUR ◽  
BEATA BUGYI ◽  
MONTSERRAT BOSCH ◽  
...  
Keyword(s):  
Molecular Motors ◽  
Molecular Mechanisms ◽  
Directed Assembly ◽  
Cellular Processes ◽  
Self Organized ◽  
Filament Assembly ◽  
Physical Measurements ◽  
Minimum Number ◽  
Broad Variety ◽  
Insight Into

Cell motility, one of the modular activities of living cells, elicits the response of the cell to extra-cellular signals, to move directionally, feed, divide or transport materials. The combined actions of molecular motors and re-modeling of the cytoskeleton generate forces and movement. Here we describe mechanistic approaches of force and movement produced by site-directed assembly of actin filaments. The insight derived from a biochemical analysis of the protein machineries involved in "actin-based motile processes" like cell protrusions, invaginations, organelle propulsion, is used to build reconstituted assays that mimic cellular processes, using several protein machineries known to initiate filament assembly by different mechanisms. Reconstitution of complex self-organized systems presents a broad variety of interests. Reconstituting actin-based movement of a functionalized particle from a minimum number of pure proteins, first used to prove the general thermodynamic principles at work in motility, then was the basis for fully controlled physical measurements of forces produced by polymerization of actin against an obstacle and of the mechanical properties of the resulting polymer arrays. In addition, measurements at the mesoscopic scale (trajectories, velocity, polymer mechanics, fluorescence of specifically labeled components of the actin array, use of mutated proteins) can provide further insight into the molecular mechanisms underlying motility.

scholarly journals Cytoskeletal actin networks in motile cells are critically self-organized systems synchronized by mechanical interactions

2011 ◽  
Vol 108 (34) ◽  
pp. 13978-13983 ◽  
Author(s):  
L. Cardamone ◽  
A. Laio ◽  
V. Torre ◽  
R. Shahapure ◽  
A. DeSimone
Keyword(s):  
Actin Networks ◽  
Self Organized ◽  
Motile Cells

scholarly journals Joining forces: crosstalk between biochemical signalling and physical forces orchestrates cellular polarity and dynamics

2018 ◽  
Vol 373 (1747) ◽  
pp. 20170145 ◽  
Author(s):  
Suvrajit Saha ◽  
Tamas L. Nagy ◽  
Orion D. Weiner
Keyword(s):  
Cell Biology ◽  
Cell Movement ◽  
Special Focus ◽  
Cellular Motility ◽  
Cellular Polarity ◽  
Self Organized ◽  
Cytoskeletal Dynamics ◽  
Physical Forces ◽  
Cytoskeletal Rearrangements

Dynamic processes like cell migration and morphogenesis emerge from the self-organized interaction between signalling and cytoskeletal rearrangements. How are these molecular to sub-cellular scale processes integrated to enable cell-wide responses? A growing body of recent studies suggest that forces generated by cytoskeletal dynamics and motor activity at the cellular or tissue scale can organize processes ranging from cell movement, polarity and division to the coordination of responses across fields of cells. To do so, forces not only act mechanically but also engage with biochemical signalling. Here, we review recent advances in our understanding of this dynamic crosstalk between biochemical signalling, self-organized cortical actomyosin dynamics and physical forces with a special focus on the role of membrane tension in integrating cellular motility. This article is part of the theme issue ‘Self-organization in cell biology’.

scholarly journals Actin and microtubule cross talk mediates persistent polarized growth

2018 ◽  
Vol 217 (10) ◽  
pp. 3531-3544 ◽  
Author(s):  
Shu-Zon Wu ◽  
Magdalena Bezanilla
Keyword(s):  
Cell Expansion ◽  
Feedback Loop ◽  
Actin Polymerization ◽  
Physcomitrella Patens ◽  
Polarized Growth ◽  
Cellular Processes ◽  
Functional Connections ◽  
Class Viii ◽  
Direct Localization ◽  
Open Question

Coordination between actin and microtubules is important for numerous cellular processes in diverse eukaryotes. In plants, tip-growing cells require actin for cell expansion and microtubules for orientation of cell expansion, but how the two cytoskeletons are linked is an open question. In tip-growing cells of the moss Physcomitrella patens, we show that an actin cluster near the cell apex dictates the direction of rapid cell expansion. Formation of this structure depends on the convergence of microtubules near the cell tip. We discovered that microtubule convergence requires class VIII myosin function, and actin is necessary for myosin VIII–mediated focusing of microtubules. The loss of myosin VIII function affects both networks, indicating functional connections among the three cytoskeletal components. Our data suggest that microtubules direct localization of formins, actin nucleation factors, that generate actin filaments further focusing microtubules, thereby establishing a positive feedback loop ensuring that actin polymerization and cell expansion occur at a defined site resulting in persistent polarized growth.

scholarly journals Fluctuation-induced distributed resonances in oscillatory networks

2019 ◽  
Vol 5 (7) ◽  
pp. eaav1027 ◽  
Author(s):  
Xiaozhu Zhang ◽  
Sarah Hallerberg ◽  
Moritz Matthiae ◽  
Dirk Witthaut ◽  
Marc Timme
Keyword(s):  
Dynamic Network ◽  
Intermediate Frequency ◽  
Response Patterns ◽  
Low Frequencies ◽  
High Frequencies ◽  
Self Organized ◽  
Oscillatory Networks ◽  
Input Signals ◽  
Induce Response ◽  
And Control

Across physics, biology, and engineering, the collective dynamics of oscillatory networks often evolve into self-organized operating states. How such networks respond to external fluctuating signals fundamentally underlies their function, yet is not well understood. Here, we present a theory of dynamic network response patterns and reveal how distributed resonance patterns emerge in oscillatory networks once the dynamics of the oscillatory units become more than one-dimensional. The network resonances are topology specific and emerge at an intermediate frequency content of the input signals, between global yet homogeneous responses at low frequencies and localized responses at high frequencies. Our analysis reveals why these patterns arise and where in the network they are most prominent. These results may thus provide general theoretical insights into how fluctuating signals induce response patterns in networked systems and simultaneously help to develop practical guiding principles for real-world network design and control.

CAN COMPLEX CELLULAR PROCESSES BE GOVERNED BY SIMPLE LINEAR RULES?

2009 ◽  
Vol 07 (01) ◽  
pp. 243-268 ◽  
Author(s):  
KUMAR SELVARAJOO ◽  
MASARU TOMITA ◽  
MASA TSUCHIYA
Keyword(s):  
Biological Networks ◽  
Biological Network ◽  
Living Systems ◽  
Regulatory Motifs ◽  
Cellular Processes ◽  
Self Organized ◽  
Wide Range ◽  
Activation Response ◽  
Physical Reasons

Complex living systems have shown remarkably well-orchestrated, self-organized, robust, and stable behavior under a wide range of perturbations. However, despite the recent generation of high-throughput experimental datasets, basic cellular processes such as division, differentiation, and apoptosis still remain elusive. One of the key reasons is the lack of understanding of the governing principles of complex living systems. Here, we have reviewed the success of perturbation–response approaches, where without the requirement of detailed in vivo physiological parameters, the analysis of temporal concentration or activation response unravels biological network features such as causal relationships of reactant species, regulatory motifs, etc. Our review shows that simple linear rules govern the response behavior of biological networks in an ensemble of cells. It is daunting to know why such simplicity could hold in a complex heterogeneous environment. Provided physical reasons can be explained for these phenomena, major advancement in the understanding of basic cellular processes could be achieved.

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