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Journal of Cell Biology

Jennifer L Brace, Matthew D Doerfler, Eric L Weiss
Eukaryotic cell division requires dependency relationships in which late processes commence only after early ones are appropriately completed. We have discovered a system that blocks late events of cytokinesis until early ones are successfully accomplished. In budding yeast, cytokinetic actomyosin ring contraction and membrane ingression are coupled with deposition of an extracellular septum that is selectively degraded in its primary septum immediately after its completion by secreted enzymes. We find this secretion event is linked to septum completion and forestalled when the process is slowed...
November 19, 2018: Journal of Cell Biology
Jakob Nilsson
The accurate segregation of genetic material to daughter cells during mitosis depends on the precise coordination and regulation of hundreds of proteins by dynamic phosphorylation. Mitotic kinases are major regulators of protein function, but equally important are protein phosphatases that balance their actions, their coordinated activity being essential for accurate chromosome segregation. Phosphoprotein phosphatases (PPPs) that dephosphorylate phosphoserine and phosphothreonine residues are increasingly understood as essential regulators of mitosis...
November 16, 2018: Journal of Cell Biology
Marit W Vermunt, Di Zhang, Gerd A Blobel
Imaging studies, high-resolution chromatin conformation maps, and genome-wide occupancy data of architectural proteins have revealed that genome topology is tightly intertwined with gene expression. Cross-talk between gene-regulatory elements is often organized within insulated neighborhoods, and regulatory cues that induce transcriptional changes can reshape chromatin folding patterns and gene positioning within the nucleus. The cause-consequence relationship of genome architecture and gene expression is intricate, and its molecular mechanisms are under intense investigation...
November 15, 2018: Journal of Cell Biology
Lena K Schroeder, Andrew E S Barentine, Holly Merta, Sarah Schweighofer, Yongdeng Zhang, David Baddeley, Joerg Bewersdorf, Shirin Bahmanyar
The endoplasmic reticulum (ER) is composed of interconnected membrane sheets and tubules. Superresolution microscopy recently revealed densely packed, rapidly moving ER tubules mistaken for sheets by conventional light microscopy, highlighting the importance of revisiting classical views of ER structure with high spatiotemporal resolution in living cells. In this study, we use live-cell stimulated emission depletion (STED) microscopy to survey the architecture of the ER at 50-nm resolution. We determine the nanoscale dimensions of ER tubules and sheets for the first time in living cells...
November 15, 2018: Journal of Cell Biology
Maria Bohnert
The lipid droplet (LD) biogenesis protein seipin is crucial for formation of normal LDs, but its exact functional role has been enigmatic. In this issue, Sui et al. (2018. J. Cell Biol. report the cryo--electron microscopy structure of seipin, which provides novel insights into how seipin might mediate LD formation.
November 15, 2018: Journal of Cell Biology
Nicole Infarinato
Mierzwa studies mechanisms of cell division in different cell types and tissue contexts.
November 14, 2018: Journal of Cell Biology
Xiaohua Hu, R Dyche Mullins
During autophagy, actin filament networks move and remodel cellular membranes to form autophagosomes that enclose and metabolize cytoplasmic contents. Two actin regulators, WHAMM and JMY, participate in autophagosome formation, but the signals linking autophagy to actin assembly are poorly understood. We show that, in nonstarved cells, cytoplasmic JMY colocalizes with STRAP, a regulator of JMY's nuclear functions, on nonmotile vesicles with no associated actin networks. Upon starvation, JMY shifts to motile, LC3-containing membranes that move on actin comet tails...
November 12, 2018: Journal of Cell Biology
Colin D H Ratcliffe, Nadeem Siddiqui, Paula P Coelho, Nancy Laterreur, Tumini N Cookey, Nahum Sonenberg, Morag Park
Differential inclusion or skipping of microexons is an increasingly recognized class of alternative splicing events. However, the functional significance of microexons and their contribution to signaling diversity is poorly understood. The Met receptor tyrosine kinase (RTK) modulates invasive growth and migration in development and cancer. Here, we show that microexon switching in the Arf6 guanine nucleotide exchange factor cytohesin-1 controls Met-dependent cell migration. Cytohesin-1 isoforms, differing by the inclusion of an evolutionarily conserved three-nucleotide microexon in the pleckstrin homology domain, display differential affinity for PI(4,5)P2 (triglycine) and PI(3,4,5)P3 (diglycine)...
November 7, 2018: Journal of Cell Biology
Liang Wang, Ziyi Yan, Helena Vihinen, Ove Eriksson, Weihuan Wang, Rabah Soliymani, Yao Lu, Yaxin Xue, Eija Jokitalo, Jing Li, Hongxia Zhao
Mitochondrial function is closely linked to its dynamic membrane ultrastructure. The mitochondrial inner membrane (MIM) can form extensive membrane invaginations known as cristae, which contain the respiratory chain and ATP synthase for oxidative phosphorylation. The molecular mechanisms regulating mitochondrial ultrastructure remain poorly understood. The Bin-Amphiphysin-Rvs (BAR) domain proteins are central regulators of diverse cellular processes related to membrane remodeling and dynamics. Whether BAR domain proteins are involved in sculpting membranes in specific submitochondrial compartments is largely unknown...
November 7, 2018: Journal of Cell Biology
Prachee Avasthi
Flagellar assembly and function depend on cargo traveling via motors on microtubule doublets. Bertiaux, Mallet et al. (2018. J. Cell Biol find that only a subset of available doublets are used for this transport in trypanosomes, leading to questions about how and why this is achieved.
November 7, 2018: Journal of Cell Biology
Nilaj Chakrabarty, Pankaj Dubey, Yong Tang, Archan Ganguly, Kelsey Ladt, Christophe Leterrier, Peter Jung, Subhojit Roy
Classic pulse-chase studies have shown that actin is conveyed in slow axonal transport, but the mechanistic basis for this movement is unknown. Recently, we reported that axonal actin was surprisingly dynamic, with focal assembly/disassembly events ("actin hotspots") and elongating polymers along the axon shaft ("actin trails"). Using a combination of live imaging, superresolution microscopy, and modeling, in this study, we explore how these dynamic structures can lead to processive transport of actin...
November 6, 2018: Journal of Cell Biology
Nathaniel Noblett, Zilu Wu, Zhao Hua Ding, Seungmee Park, Tony Roenspies, Stephane Flibotte, Andrew D Chisholm, Yishi Jin, Antonio Colavita
Neuronal morphology and circuitry established during early development must often be maintained over the entirety of animal lifespans. Compared with neuronal development, the mechanisms that maintain mature neuronal structures and architecture are little understood. The conserved disco-interacting protein 2 (DIP2) consists of a DMAP1-binding domain and two adenylate-forming domains (AFDs). We show that the Caenorhabditis elegans DIP-2 maintains morphology of mature neurons. dip-2 loss-of-function mutants display a progressive increase in ectopic neurite sprouting and branching during late larval and adult life...
November 5, 2018: Journal of Cell Biology
Kohei Nishimura, Masataka Komiya, Tetsuya Hori, Takehiko Itoh, Tatsuo Fukagawa
The centromere is an important genomic locus for chromosomal segregation. Although the centromere is specified by sequence-independent epigenetic mechanisms in most organisms, it is usually composed of highly repetitive sequences, which associate with heterochromatin. We have previously generated various chicken DT40 cell lines containing differently positioned neocentromeres, which do not contain repetitive sequences and do not associate with heterochromatin. In this study, we performed systematic 4C analysis using three cell lines containing differently positioned neocentromeres to identify neocentromere-associated regions at the 3D level...
November 5, 2018: Journal of Cell Biology
Fengrong Wang, Song Chen, Hans B Liu, Carole A Parent, Pierre A Coulombe
The a and b isoforms of keratin 6 (K6), a type II intermediate filament (IF) protein, are robustly induced upon injury to interfollicular epidermis. We previously showed that complete loss of K6a/K6b stimulates keratinocyte migration, correlating with enhanced Src activity. In this study, we demonstrate that this property is cell autonomous, depends on the ECM, and results from elevated speed, enhanced directionality, and an increased rate of focal adhesion disassembly. We show that myosin IIA interacts with K6a/K6b, that its levels are markedly reduced in Krt6a/Krt6b -null keratinocytes, and that inhibiting myosin ATPase activity normalizes the enhanced migration potential of Krt6a/Krt6b -null cells...
November 2, 2018: Journal of Cell Biology
Jelmer J Lindeboom, Masayoshi Nakamura, Marco Saltini, Anneke Hibbel, Ankit Walia, Tijs Ketelaar, Anne Mie C Emons, John C Sedbrook, Viktor Kirik, Bela M Mulder, David W Ehrhardt
Central to the building and reorganizing cytoskeletal arrays is creation of new polymers. Although nucleation has been the major focus of study for microtubule generation, severing has been proposed as an alternative mechanism to create new polymers, a mechanism recently shown to drive the reorientation of cortical arrays of higher plants in response to blue light perception. Severing produces new plus ends behind the stabilizing GTP-cap. An important and unanswered question is how these ends are stabilized in vivo to promote net microtubule generation...
October 30, 2018: Journal of Cell Biology
Mara A Olenick, Roberto Dominguez, Erika L F Holzbaur
Axonal transport is required for neuronal development and survival. Transport from the axon to the soma is driven by the molecular motor cytoplasmic dynein, yet it remains unclear how dynein is spatially and temporally regulated. We find that the dynein effector Hook1 mediates transport of TrkB-BDNF-signaling endosomes in primary hippocampal neurons. Hook1 comigrates with a subpopulation of Rab5 endosomes positive for TrkB and BDNF, which exhibit processive retrograde motility with faster velocities than the overall Rab5 population...
October 29, 2018: Journal of Cell Biology
Francis J McNally, Antonina Roll-Mecak
Microtubule-severing enzymes generate internal breaks in microtubules. They are conserved in eukaryotes from ciliates to mammals, and their function is important in diverse cellular processes ranging from cilia biogenesis to cell division, phototropism, and neurogenesis. Their mutation leads to neurodegenerative and neurodevelopmental disorders in humans. All three known microtubule-severing enzymes, katanin, spastin, and fidgetin, are members of the meiotic subfamily of AAA ATPases that also includes VPS4, which disassembles ESCRTIII polymers...
October 29, 2018: Journal of Cell Biology
Henrik J Jürgensen, Kirstine S Nørregaard, Megan M Sibree, Eric Santoni-Rugiu, Daniel H Madsen, Katharina Wassilew, Dorrit Krustrup, Peter Garred, Thomas H Bugge, Lars H Engelholm, Niels Behrendt
Collectins such as mannose-binding lectin (MBL) and surfactant protein D (SP-D) become temporarily deposited in extravascular compartments after tissue injury and perform immune-stimulatory or inflammation-limiting functions. However, their turnover mechanisms, necessary to prevent excessive tissue damage, are virtually unknown. In this study, we show that fibroblasts in injured tissues undertake the clearance of collectins by using the endocytic collagen receptor uPARAP. In cellular assays, several types of collectins were endocytosed in a highly specific uPARAP-dependent process, not shared by the closely related receptor MR/CD206...
October 26, 2018: Journal of Cell Biology
Richa Sardana, Lu Zhu, Scott D Emr
Maintenance of organelle identity is profoundly dependent on the coordination between correct targeting of proteins and removal of mistargeted and damaged proteins. This task is mediated by organelle-specific protein quality control (QC) systems. In yeast, the endocytosis and QC of most plasma membrane (PM) proteins requires the Rsp5 ubiquitin ligase and ART adaptor network. We show that intracellular adaptors of Rsp5, Ear1, and Ssh4 mediate recognition and vacuolar degradation of PM proteins that escape or bypass PM QC systems...
October 25, 2018: Journal of Cell Biology
Stéphanie Torrino, Wei-Wei Shen, Cédric M Blouin, Satish Kailasam Mani, Christine Viaris de Lesegno, Pierre Bost, Alexandre Grassart, Darius Köster, Cesar Augusto Valades-Cruz, Valérie Chambon, Ludger Johannes, Paolo Pierobon, Vassili Soumelis, Catherine Coirault, Stéphane Vassilopoulos, Christophe Lamaze
Caveolae are small invaginated pits that function as dynamic mechanosensors to buffer tension variations at the plasma membrane. Here we show that under mechanical stress, the EHD2 ATPase is rapidly released from caveolae, SUMOylated, and translocated to the nucleus, where it regulates the transcription of several genes including those coding for caveolae constituents. We also found that EHD2 is required to maintain the caveolae reservoir at the plasma membrane during the variations of membrane tension induced by mechanical stress...
October 22, 2018: Journal of Cell Biology
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