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Current Opinion in Cell Biology

Yu-Ju Chen, Carlo Giovanni Quintanilla, Jen Liou
ER-PM junctions are subcellular sites where the endoplasmic reticulum (ER) and the plasma membrane (PM) are kept in close appositions, providing a platform for inter-organelle contact. These membrane contact sites are important for many physiological functions in mammalian cells, including excitation-contraction coupling, store-operated Ca2+ entry, and non-vesicular transfer of lipids between the ER and the PM. Here we review recent insights into the 3D structure and spatial organization of ER-PM junctions in mammalian cells as well as molecular mechanisms underlying the formation and functions of mammalian ER-PM junctions...
February 7, 2019: Current Opinion in Cell Biology
Ruoyi Qiu, Richard S Lewis
Store-operated calcium entry (SOCE) through Orai channels is triggered by receptor-stimulated depletion of Ca2+ from the ER. Orai1 is unique in terms of its activation mechanism, biophysical properties, and structure, and its precise regulation is essential for human health. Recent studies have begun to reveal the structural basis of the major steps in the SOCE pathway and how the system is reliably suppressed in resting cells but able to respond robustly to ER Ca2+ depletion. In this review, we discuss current models describing the activation of ER Ca2+ sensor STIM1, its binding to Orai1, propagation of the binding signal from the channel periphery to the central pore, and the resulting conformational changes underlying opening of the highly Ca2+ selective Orai1 channel...
February 1, 2019: Current Opinion in Cell Biology
Zara Y Weinberg, Stephanie E Crilly, Manojkumar A Puthenveedu
Several GPCRs, including receptors previously thought to signal primarily from the cell surface, have been recently shown to signal from many intracellular compartments. This raises the idea that signaling by any given receptor is spatially encoded in the cell, with distinct sites of signal origin dictating distinct downstream consequences. We will discuss recent developments that address this novel facet of GPCR physiology, focusing on the spatial segregation of signaling from the cell surface, endosomes, and the Golgi by receptors relevant to the nervous system...
January 29, 2019: Current Opinion in Cell Biology
Hironori Funabiki
For equal chromosome segregation, a pair of kinetochores on each duplicated chromosome must attach to microtubules connecting to opposite poles. The protein kinase Aurora B plays a critical role in destabilizing microtubules attached in a wrong orientation through phosphorylating kinetochore proteins. The mechanism behind this selective destabilization of aberrant attachments remains elusive. While Aurora B is most enriched on the centromere from prophase to metaphase, emerging evidence suggests the importance of Aurora B on microtubules in this process...
January 22, 2019: Current Opinion in Cell Biology
Natarin Caengprasath, Aylin C Hanyaloglu
The pivotal and diverse roles G protein-coupled receptors (GPCRs) play in physiology are matched by the increasingly complex signal systems they activate. Over the past decade, our models of GPCR signaling systems also include a vital role of location in controlling GPCR signaling, whereby plasma membrane, clathrin-associated structures and a diverse endomembrane network provide highly specialized signal platforms for this superfamily of receptors. The aim of this review is to highlight the recent developments in this fast-evolving field, with particular emphasis on endocrine-relevant GPCRs...
January 22, 2019: Current Opinion in Cell Biology
Tatsuro Yamamoto, Noriko Saitoh
Large-scale transcriptome analyses have identified a variety of non-coding RNAs (ncRNAs) that are not translated into proteins. Many of them are in the nucleus, where they associate with chromatin and regulate its structure and function. Interphase chromosomes are intricately folded into multiple layers and composed of domains. Recent studies using Hi-C technologies have identified a mega-base self-associating chromatin domain: the topologically associating domain (TAD). The domain boundaries are demarcated with the chromatin regulatory proteins CTCF and cohesin, which are often bound to or recruited by ncRNAs...
January 22, 2019: Current Opinion in Cell Biology
Junichirou Ohzeki, Vladimir Larionov, William C Earnshaw, Hiroshi Masumoto
Accurate chromosome segregation is essential for cell proliferation. The centromere is a specialized chromosomal locus, on which the kinetochore structure is formed. The centromere/kinetochore is required for the equal separation of sister chromatids to daughter cells. Here, we review recent findings on centromere-specific chromatin, including its constitutive protein components, its de novo formation and maintenance mechanisms, and our progress in analyses with synthetic human artificial chromosomes (HACs)...
January 14, 2019: Current Opinion in Cell Biology
Dennis Zimmermann, David R Kovar
Fundamental cellular processes such as division, polarization, and motility require the tightly regulated spatial and temporal assembly and disassembly of the underlying actin cytoskeleton. The actin cytoskeleton has been long viewed as a central player facilitating diverse mechanotransduction pathways due to the notion that it is capable of receiving, processing, transmitting, and generating mechanical stresses. Recent work has begun to uncover the roles of mechanical stresses in modulating the activity of key regulatory actin-binding proteins and their interactions with actin filaments, thereby controlling the assembly (formin and Arp2/3 complex) and disassembly (ADF/Cofilin) of actin filament networks...
January 10, 2019: Current Opinion in Cell Biology
Maria Almonacid, Marie-Emilie Terret, Marie-Hélène Verlhac
Cells are the building units of living organisms and consequently adapt to their environment by modulating their intracellular architecture, in particular the position of their nucleus. Important efforts have been made to decipher the molecular mechanisms involved in nuclear positioning. The LINC complex at the nuclear envelope is a very important part of the molecular connectivity between the cell outside and the intranuclear compartment, and thus emerged as a central player in nuclear mechanotransduction...
December 26, 2018: Current Opinion in Cell Biology
Johanna Ivaska, Manuel Théry
No abstract text is available yet for this article.
December 21, 2018: Current Opinion in Cell Biology
Carmelina Petrungaro, Benoît Kornmann
Over the last years, the importance of inter-organelle communication has become more and more evident, attested by the fast growing number of newly-identified membrane contact sites (MCS). At MCSs two organelles are connected via protein tethers that bring them in close proximity to facilitate metabolite exchange. In this review, we will focus on the MCSs connecting the ER and mitochondria, which have been implicated in phospholipid transport. While we already know the molecular identity of some tethers, we are still far from understanding the mechanisms underlying the phospholipid transport processes...
December 13, 2018: Current Opinion in Cell Biology
G V Shivashankar
Landmark experiments in vitro showed that somatic cells can be reprogrammed to stem-cells by the constitutive expression of particular transcription factors. However, in vivo cells naturally exhibit de-differentiation and trans-differentiation programs, thereby suggesting that the signals from the local mechanical microenvironment may be sufficient to induce stem-cell state transitions. In this review, we discuss recent evidence for the biophysical regulation of genome architecture and nuclear programs. We start by discussing the coupling between cellular architecture, genome organization and gene expression...
December 13, 2018: Current Opinion in Cell Biology
Tomoko Nishiyama
Cohesin, one of structural maintenance of chromosomes (SMC) complexes, forms a ring-shaped protein complex, and mediates sister chromatid cohesion for accurate chromosome segregation and precise genome inheritance. The cohesin ring entraps one or two DNA molecules to achieve cohesion, which is further regulated by cohesin-binding proteins and modification enzymes in a cell cycle-dependent manner. Recent significant advancements in Hi-C technologies have revealed numerous cohesin-dependent higher-order chromatin structures...
December 10, 2018: Current Opinion in Cell Biology
Imke Baade, Ralph H Kehlenbach
The molecular mechanisms of nuclear transport have been described in great detail and we are beginning to understand the structures of transport complexes and even of subcomplexes of the nuclear pore at an atomic or near-atomic resolution. The complexity of the clients that use the transport machinery, by contrast, is less well understood, although some transport receptors are reported to have hundreds of different cargoes and others only a few. Here, we review the recent attempts to define the cargo spectrum of individual nuclear transport receptors using bioinformatic, biochemical and cell biological approaches and compare the results obtained by these complementary methods...
December 6, 2018: Current Opinion in Cell Biology
Davide Calebiro, Marie-Lise Jobin
G protein-coupled receptors (GPCRs) are among the best-studied membrane receptors, mainly due to their central role in human physiology, involvement in disease and relevance as drug targets. Although biochemical and pharmacological studies have characterized the main steps in GPCR signaling, how GPCRs produce highly specific responses in our cells remains insufficiently understood. New developments in single-molecule microscopy have made it possible to study the protein-protein interactions at the basis of GPCR signaling in previously inconceivable detail...
December 3, 2018: Current Opinion in Cell Biology
Peter J Foster, Sebastian Fürthauer, Michael J Shelley, Daniel J Needleman
Many subcellular structures contain large numbers of cytoskeletal filaments. Such assemblies underlie much of cell division, motility, signaling, metabolism, and growth. Thus, understanding cell biology requires understanding the properties of networks of cytoskeletal filaments. While there are well established disciplines in biology dedicated to studying isolated proteins - their structure (Structural Biology) and behaviors (Biochemistry) - it is much less clear how to investigate, or even just describe, the structure and behaviors of collections of cytoskeletal filaments...
November 27, 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...
February 2019: Current Opinion in Cell Biology
Katja Röper, Xosé R Bustelo
No abstract text is available yet for this article.
December 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...
December 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...
December 2018: Current Opinion in Cell Biology
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