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Current Opinion in Cell Biology

Robert A Cross
In classical microtubule dynamic instability, the dynamics of the built polymer depend only on the nucleotide state of its individual tubulin molecules. Recent work is overturning this view, pointing instead towards lattice plasticity, in which the fine-structure and mechanics of the microtubule lattice are emergent properties that depend not only on the nucleotide state of each tubulin, but also on the nucleotide states of its neighbours, on its and their isotypes, and on interacting proteins, drugs, local mechanical strain, post translational modifications, packing defects and solvent conditions...
November 8, 2018: Current Opinion in Cell Biology
Ivana Gasic, Timothy J Mitchison
Even in the face of damaging insults, most cells maintain stability over time through multiple homeostatic pathways, including maintenance of the microtubule cytoskeleton that is fundamental to numerous cellular processes. The dynamic instability-perpetual growth and shrinkage-is the best-known microtubule regulatory pathway, which allows rapid rebuilding of the microtubule cytoskeleton in response to internal or external cues. Much less investigated is homeostatic regulation through availability of α-β tubulin heterodimers-microtubules' main building blocks-which influences total mass and dynamic behavior of microtubules...
November 8, 2018: Current Opinion in Cell Biology
K Tanuj Sapra, Patrizia M Spoerri, Andreas Engel, David Alsteens, Daniel J Müller
G protein-coupled receptors (GPCRs) relay extracellular information across cell membranes through a continuum of conformations that are not always captured in structures. Hence, complementary approaches are required to quantify the physical and chemical properties of the dynamic conformations linking to GPCR function. Atomic force microscopy (AFM)-based high-resolution imaging and force spectroscopy are unique methods to scrutinize GPCRs and to sense their interactions. Here, we exemplify recent AFM-based applications to directly observe the supramolecular assembly of GPCRs in native membranes, to measure the ligand-binding free-energy landscape, and how interactions modulate the structural properties of GPCRs...
November 6, 2018: Current Opinion in Cell Biology
Raphael Silvanus Haider, Amod Godbole, Carsten Hoffmann
Advances in resolving crystal structures of GPCRs and their binding partners as well as improvements in live-cell microscopy and the fluorescent proteins pallet has greatly driven new ideas for designing optical sensors for the same. Sensors have been developed to monitor ligand binding as well as the ensuing ligand-induced conformational changes in GPCRs, G-proteins and arrestins. In this review we will highlight the functionality of such sensor designs starting from monitoring ligand binding to receptor activation and interaction with arrestins...
November 5, 2018: Current Opinion in Cell Biology
Bruno Mesmin, David Kovacs, Giovanni D'Angelo
Meticulous observations of the cell perinuclear region where the Golgi and the endoplasmic reticulum (ER) networks intermingle have revealed close contact sites of barely 20 nm between these two organelles. Recent studies demonstrate that molecular machineries, including lipid-transfer proteins, enriched in membrane contact sites between ER and trans-Golgi are capable of bridging membranes and exchanging key lipids such as sphingolipid precursors and cholesterol while bypassing the early secretory compartments...
October 31, 2018: Current Opinion in Cell Biology
Colin W Taylor, Khaled Machaca
Inositol 1,4,5-trisphosphate receptors (IP3 Rs) are widely expressed intracellular Ca2+ channels that evoke large local increases in cytosolic Ca2+ concentration. By depleting the ER of Ca2+ , IP3 Rs also activate store-operated Ca2+ entry (SOCE). Immobile IP3 Rs close to the plasma membrane (PM) are the only IP3 Rs that respond to physiological stimuli. The association of these 'licensed' IP3 Rs with the ER-PM junctions where STIM interacts with Orai PM Ca2+ channels may define the autonomous functional unit for SOCE...
October 24, 2018: Current Opinion in Cell Biology
Jorge Barbazán, Danijela Matic Vignjevic
The most abundant cell type in the tumor microenvironment are cancer-associated fibroblasts (CAFs). CAFs play an important role in tumor growth and progression. Besides direct communication with cancer cells via secreted molecules or cell-cell adhesions, CAFs also indirectly affect cancer cell behavior by remodeling the extracellular matrix (ECM). Here, we summarize recent findings on the distinct mechanisms that CAFs use to modify ECM, specifically, their proteolytic versus force-dependent activity. We then review the consequences of CAF force transmission on the physico-chemical properties of the matrix, focusing on the deposition of new matrix components, and the alteration of the organization and stiffness of the ECM...
October 8, 2018: Current Opinion in Cell Biology
Harry Warner, Beverley J Wilson, Patrick T Caswell
Cell migration is a critical process that underpins a number of physiological and pathological contexts such as the correct functioning of the immune system and the spread of metastatic cancer cells. Central to this process are the Rho family of GTPases, which act as core regulators of cell migration. Rho GTPases are molecular switches that associate with lipid membranes and act to choreograph molecular events that underpin cell migration. Specifically, these GTPases play critical roles in coordinating force generation through driving the formation of cellular protrusions as well as cell-cell and cell-matrix adhesions...
October 3, 2018: Current Opinion in Cell Biology
Katja Röper, Xosé R Bustelo
No abstract text is available yet for this article.
October 1, 2018: Current Opinion in Cell Biology
Klemens Rottner, Matthias Schaks
Cell migration entails a plethora of activities combining the productive exertion of protrusive and contractile forces to allow cells to push and squeeze themselves through cell clumps, interstitial tissues or tissue borders. All these activities require the generation and turnover of actin filaments that arrange into specific, subcellular structures. The most prominent structures mediating the protrusion at the leading edges of cells include lamellipodia and filopodia as well as plasma membrane blebs. Moreover, in cells migrating on planar substratum, mechanical support is being provided by an additional, more proximally located structure termed the lamella...
September 29, 2018: Current Opinion in Cell Biology
Nilay Taneja, Lindsay Rathbun, Heidi Hehnly, Dylan T Burnette
The ability to divide is a fundamental property of a living cell. The 3D orientation of cell division is essential for embryogenesis, maintenance of tissue organization and architecture, as well as controlling cell fate. Much attention has been placed on the mitotic spindle's role in placing itself along the cell's longest axis, where a shape sensing mechanism between a population of microtubules extending from mitotic centrosomes to the cell cortex occurs. However, contractile forces at the cell cortex also likely play a decisive role in determining the final placement of daughter cells following division...
September 27, 2018: Current Opinion in Cell Biology
Samuel Mathieu, Jean-Baptiste Manneville
Cell mechanics is crucial for a wide range of cell functions, including proliferation, polarity, migration and differentiation. Cells sense external physical cues and translate them into a cellular response. While force sensing occurs in the vicinity of the plasma membrane, forces can reach deep in the cell interior and to the nucleus. We review here the recent developments in the field of intracellular mechanics. We focus first on intracellular rheology, the study of the mechanical properties of the cell interior, and recapitulate the contribution of active mechanisms, the cytoskeleton and intracellular organelles to cell rheology...
September 22, 2018: Current Opinion in Cell Biology
Boris Simonetti, Peter J Cullen
Endosomes constitute major sorting compartments within the cell. There, a myriad of transmembrane proteins (cargoes) are delivered to the lysosome for degradation or retrieved from this fate and recycled through tubulo-vesicular transport carriers to different cellular destinations. Retrieval and recycling are orchestrated by multi-protein assemblies that include retromer and retriever, sorting nexins, and the Arp2/3 activating WASH complex. Fine-tuned control of actin polymerization on endosomes is fundamental for the retrieval and recycling of cargoes...
September 15, 2018: Current Opinion in Cell Biology
Esha Madan, Rajan Gogna, Eduardo Moreno
Cell competition is a biological mechanism conserved from Drosophila to vertebrates wherein neighboring cells compare their relative fitness status resulting in the elimination of less fit cells by those with higher fitness. This is an active process that is essential for embryonic and organ development, tissue homeostasis, delay of ageing and in various disease models such as cancer. Recent research is beginning to unravel the various mechanisms of cell competition and the sensing of fitness status. Fitness fingerprints, death receptors, mechanical cell competition and a set of unknown genetic or signaling pathways are emerging as important pathways governing the mechanisms for cell to compare their relative fitness levels...
September 9, 2018: Current Opinion in Cell Biology
Jonathan D Humphries, Megan R Chastney, Janet A Askari, Martin J Humphries
Integrin adhesion complexes (IACs) have evolved over millions of years to integrate metazoan cells physically with their microenvironment. It is presumed that the simultaneous interaction of thousands of integrin receptors to binding sites in anisotropic extracellular matrix (ECM) networks enables cells to assemble a topological description of the chemical and mechanical properties of their surroundings. This information is then converted into intracellular signals that influence cell positioning, differentiation and growth, but may also influence other fundamental processes, such as protein synthesis and energy regulation...
September 5, 2018: Current Opinion in Cell Biology
Yosuke Senju, Pekka Lappalainen
The actin cytoskeleton is indispensable for several cellular processes, including migration, morphogenesis, polarized growth, endocytosis, and phagocytosis. The organization and dynamics of the actin cytoskeleton in these processes are regulated by Rho family small GTPases and kinase-phosphatase pathways. Moreover, membrane phospholipids, especially the phosphatidylinositol phosphates have emerged as important regulators of actin dynamics. From these, PI(4,5)P2 is the most abundant at the plasma membrane, and directly regulates the activities and subcellular localizations of numerous actin-binding proteins...
September 4, 2018: Current Opinion in Cell Biology
Matthias Plessner, Robert Grosse
While it is long known that actin is part of the nuclear proteome, its properties and functions as regulated, functional and dynamically assembled actin filaments are only recently emerging. Thus, newly uncovered roles for intranuclear actin filaments are opening new perspectives on how the nucleus and its genomic content may be organized in particular with regard to a given stage of the cell cycle. Here, we summarize recent studies on actin filament polymerization and turnover within the nuclear compartment of mammalian cells...
September 4, 2018: Current Opinion in Cell Biology
Westley Heydeck, Lorraine Fievet, Erica E Davis, Nicholas Katsanis
Cilia are microtubule-based appendages present on almost all vertebrate cell types where they mediate a myriad of cellular processes critical for development and homeostasis. In humans, impaired ciliary function is associated with an ever-expanding repertoire of phenotypically-overlapping yet highly variable genetic disorders, the ciliopathies. Extensive work to elucidate the structure, function, and composition of the cilium is offering hints that the `static' representation of the cilium is a gross oversimplification of a highly dynamic organelle whose functions are choreographed dynamically across cell types, developmental, and homeostatic contexts...
August 20, 2018: Current Opinion in Cell Biology
Vania Mm Braga, Andrew J Ewald
No abstract text is available yet for this article.
October 2018: Current Opinion in Cell Biology
Nan-Peng Chen, Zhiqi Sun, Reinhard Fässler
Integrin-mediated cell adhesion plays key roles for cell movement during development and tissue homeostasis. The dynamic life cycle of various integrin adhesions structures is required for the cell movements and regulated by the coordinated actions of both actomyosin and the microtubule (MT) cytoskeleton. The evolutionarily conserved Kank family proteins have emerged as regulators of adhesion dynamics by coordinating integrin-mediated force transmission with the recruitment of microtubules to integrins. These novel functions may play important roles in vivo and in human diseases...
October 2018: Current Opinion in Cell Biology
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