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Molecular Biology of the Cell

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https://read.qxmd.com/read/30865564/integrin-%C3%AE-6%C3%AE-4e-variant-is-associated-with-actin-and-cd9-structures-and-modifies-the-biophysical-properties-of-cell-cell-and-cell-ecm-interactions
#1
Mengdie Wang, James P Hinton, Jaime M C Gard, Joe G N Garcia, Beatrice S Knudsen, Raymond B Nagle, Anne E Cress
Integrin α6β4 is an essential, dynamic adhesion receptor for laminin 332 found on epithelial cells, required for formation of strong cell-ECM adhesion and induced migration, and coordinated by regions of the β4C cytoplasmic domain. β4E, a unique splice variant of β4 expressed in normal tissue, contains a cytoplasmic domain of 231 amino acids with a unique 114 amino acids sequence instead of β4C's canonical 1089 amino acids. We determined the distribution of α6β4E within normal human glandular epithelium and its regulation and effect on cellular biophysical properties...
March 13, 2019: Molecular Biology of the Cell
https://read.qxmd.com/read/30865562/stretching-magnitude-dependent-inactivation-of-akt-by-ros-led-to-enhanced-p53-mitochondrial-translocation-and-myoblasts-apoptosis
#2
Song Jing, Wang Yaqi, Yuan Xiao, Ji Qiuxia, Fan Cunhui, Zhao Hongmei, Hao Wenjing, Ren Dapeng
Previously, we had shown that high magnitude stretch (HMS), rather than low magnitude stretch (LMS), induced significant apoptosis of skeletal muslce C2C12 myoblasts. However, the molecular mechanism remains obscure. In this study, we found that p53 protein accumulated in nucleus of LMS-loaded cells, while it translocated into mitochondria of HMS-loaded cells. Knocking down endogenous p53 by shRNA abrogated HMS-induced apoptosis. Furthermore, we demonstrated that over-accumulation of ROS during HMS inactivated AKT that was activated in LMS-treated cells, which accounted for the distinct p53 subcellular localizations under HMS and LMS...
March 13, 2019: Molecular Biology of the Cell
https://read.qxmd.com/read/30865560/myosin-ii-governs-intracellular-pressure-and-traction-by-distinct-tropomyosin-dependent-mechanisms
#3
Kimheak Sao, Tia M Jones, Andrew D Doyle, Debonil Maity, Galina Schevzov, Yun Chen, Peter W Gunning, Ryan J Petrie
Two-dimensional (2D) substrate rigidity promotes myosin II activity to increase traction force in a process negatively regulated by tropomyosin (Tpm) 2.1. We recently discovered that actomyosin contractility can increase intracellular pressure and switch tumor cells from low-pressure lamellipodia to high-pressure lobopodial protrusions during 3D migration. However, it remains unclear whether these myosin II-generated cellular forces are produced simultaneously, and by the same molecular machinery. Here we identify Tpm 1...
March 13, 2019: Molecular Biology of the Cell
https://read.qxmd.com/read/30865555/elmod2-regulates-mitochondrial-fusion-in-a-mitofusin-dependent-manner-downstream-of-arl2
#4
Cara R Schiavon, Rachel E Turn, Laura E Newman, Richard A Kahn
Mitochondria are essential and dynamic organelles, undergoing constant fission and fusion. The primary players in mitochondrial morphology (MFN1/2, OPA1, DRP1) have been identified, but their mechanism(s) of regulation are still being elucidated. ARL2 is a regulatory GTPase which has previously been shown to play a role in the regulation of mitochondrial morphology. Here we demonstrate that ELMOD2, an ARL2 GTPase activating protein (GAP), is necessary for ARL2 to promote mitochondrial elongation. We show that loss of ELMOD2 causes mitochondrial fragmentation and a lower rate of mitochondrial fusion, while ELMOD2 overexpression promotes mitochondrial tubulation and increases the rate of fusion in a mitofusin-dependent fashion...
March 13, 2019: Molecular Biology of the Cell
https://read.qxmd.com/read/30865554/tgcep250-is-dynamically-processed-through-the-division-cycle-and-essential-for-structural-integrity-of-the-toxoplasma-centrosome
#5
Chun-Ti Chen, Marc-Jan Gubbels
The apicomplexan centrosome has a unique bipartite structure comprising an inner- and outer-core responsible for the nuclear cycle (mitosis) and budding cycles (cytokinesis), respectively. Although these two cores are always associated, they function independently to facilitate polyploid intermediates in the production of many progeny per replication round. Here, we describe the function of a large coiled-coil protein in Toxoplasma gondii, TgCep250, in connecting the two centrosomal cores and promoting their structural integrity...
March 13, 2019: Molecular Biology of the Cell
https://read.qxmd.com/read/30840554/pp2a-b55-sur-6-collaborates-with-the-nuclear-lamina-for-centrosome-separation-during-mitotic-entry
#6
Vincent Boudreau, Richard Chen, Alan Edwards, Muhammad Sulaimain, Paul S Maddox
Across most sexually reproducing animals, centrosomes are provided to the oocyte through fertilization and must be positioned properly to establish the zygotic mitotic spindle. How centrosomes are positioned in space and time through the concerted action of key mitotic entry biochemical regulators including Protein Phosphatase 2A (PP2A-B55/SUR-6), biophysical regulators including Dynein, and the nuclear lamina is unclear. Here, we uncover a role for PP2A-B55/SUR-6 in regulating centrosome separation. Mechanistically, PP2A-B55/SUR-6 regulates nuclear size prior to mitotic entry, in turn affecting nuclear envelope-based Dynein density and motor capacity...
March 6, 2019: Molecular Biology of the Cell
https://read.qxmd.com/read/30840538/nestin-in-immature-embryonic-neurons-affects-axon-growth-cone-morphology-and-semaphorin3a-sensitivity
#7
C J Bott, C G Johnson, C C Yap, N D Dwyer, K A Litwa, B Winckler
Correct wiring in the neocortex requires that responses to an individual guidance cue vary among neurons in the same location, and within the same neuron over time. Nestin is an atypical intermediate filament expressed highly in neural progenitors and is thus used widely as a progenitor marker. Here we show a subpopulation of embryonic cortical neurons which transiently express nestin in their axons. Nestin expression is thus not restricted to neural progenitors but persists for 2-3 days at lower levels in newborn neurons...
March 6, 2019: Molecular Biology of the Cell
https://read.qxmd.com/read/30840537/retromer-facilitates-the-localization-of-bcl-xl-to-the-mitochondrial-outer-membrane
#8
Trey Farmer, Katelyn L O'Neill, Naava Naslavsky, Xu Luo, Steve Caplan
The anti-apoptotic Bcl-2 family protein Bcl-xL plays a critical role in cell survival by protecting the integrity of the mitochondrial outer membrane (MOM). The mechanism through which Bcl-xL is recruited to the MOM has not been fully discerned. The retromer is a conserved endosomal scaffold complex involved in membrane trafficking.  Here we identify VPS35 and VPS26, two core components of the retromer, as novel regulators of Bcl-xL. We observed interactions and co-localization between Bcl-xL, VPS35, VPS26 and MICAL-L1, a protein involved in recycling endosome biogenesis that also interacts with the retromer...
March 6, 2019: Molecular Biology of the Cell
https://read.qxmd.com/read/30811273/ehd2-regulates-adipocyte-function-and-is-enriched-at-cell-surface-associated-lipid-droplets-in-primary-human-adipocytes
#9
Björn Morén, Björn Hansson, Florentina Negoita, Claes Fryklund, Richard Lundmark, Olga Göransson, Karin G Stenkula
Adipocytes play a central role in energy balance, and dysfunctional adipose tissue severely affects systemic energy homeostasis. The ATPase EH domain-containing 2 (EHD2) has previously been shown to regulate caveolae, plasma membrane-specific domains that are involved in lipid uptake and signal transduction. Here, we investigated the role of EHD2 in adipocyte function. We demonstrate that EHD2 protein expression is highly upregulated at the onset of triglyceride accumulation during adipocyte differentiation...
February 27, 2019: Molecular Biology of the Cell
https://read.qxmd.com/read/30811271/syntaxin-11-regulates-the-stimulus-dependent-transport-of-toll-like-receptor-4-to-the-plasma-membrane-by-cooperating-with-snap-23-in-macrophages
#10
Daiki Kinoshita, Chiye Sakurai, Maya Morita, Masashi Tsunematsu, Naohiro Hori, Kiyotaka Hatsuzawa
Syntaxin 11 (stx11) is a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) that is selectively expressed in immune cells; however, its precise role in macrophages is unclear. We showed that stx11 knockdown reduces the phagocytosis of Escherichia coli in interferon-γ-activated macrophages. Stx11 knockdown decreased toll-like receptor 4 (TLR4) localization on the plasma membrane without affecting total expression. Plasma membrane-localized TLR4 was primarily endocytosed within 1 hour by lipopolysaccharide (LPS) stimulation and gradually re-localized 4 hours after removal of LPS...
February 27, 2019: Molecular Biology of the Cell
https://read.qxmd.com/read/30811270/regulation-of-lc3-lipidation-by-the-autophagy-specific-class-iii-phosphatidylinostitol-3-kinase-complex
#11
Livia W Brier, Liang Ge, Goran Stjepanovic, Ashley M Thelen, James Hurley, Randy Schekman
Autophagy is a conserved eukaryotic pathway critical for cellular adaptation to changes in nutrition levels and stress. The class III phosphatidylinositol 3-kinase complexes I and II (PI3KC3-C1 and C2) are essential for autophagosome initiation and maturation, respectively, from highly curved vesicles. We used a cell-free reaction that reproduces a key autophagy initiation step, LC3 lipidation, as a biochemical readout to probe the role of ATG14, a PI3KC3-C1-specific subunit implicated in targeting the complex to autophagy initiation sites...
February 27, 2019: Molecular Biology of the Cell
https://read.qxmd.com/read/30811267/cep135-isoform-dysregulation-promotes-centrosome-amplification-in-breast-cancer-cells
#12
Divya Ganapathi Sankaran, Alexander J Stemm-Wolf, Chad G Pearson
The centrosome, comprised of two centrioles surrounded by pericentriolar material, is the cell's central microtubule organizing center. Centrosome duplication is coupled with the cell cycle such that centrosomes duplicate once in S phase. Loss of such coupling produces supernumerary centrosomes, a condition called centrosome amplification (CA). CA promotes cell invasion and chromosome instability, two hallmarks of cancer. We examined the contribution of centriole overduplication to CA and the consequences for genomic stability in breast cancer cells...
February 27, 2019: Molecular Biology of the Cell
https://read.qxmd.com/read/30811261/lymphatic-endothelial-cell-calcium-pulses-are-sensitive-to-spatial-gradients-in-wall-shear-stress
#13
Vinay N Surya, Eleftheria Michalaki, Gerald G Fuller, Alexander R Dunn
Cytosolic calcium (Ca2+ ) is a ubiquitous second messenger that influences numerous aspects of cellular function. In many cell types cytosolic Ca2+ concentrations are characterized by periodic pulses whose dynamics can influence downstream signal transduction. Here, we examined the general question of how cells use Ca2+ pulses to encode input stimuli in the context of the response of lymphatic endothelial cells (LECs) to fluid flow. Previous work shows that fluid flow regulates Ca2+ dynamics in LECs, and that Ca2+ -dependent signaling plays a key role in regulating lymphatic valve formation during embryonic development...
February 27, 2019: Molecular Biology of the Cell
https://read.qxmd.com/read/30785867/isoform-specific-ras-signaling-is-growth-factor-dependent
#14
Fiona E Hood, Bertram Klinger, Anna U Newlaczyl, Anja Sieber, Mathurin Dorel, Simon P Oliver, Judy M Coulson, Nils Blüthgen, Ian A Prior
HRAS, NRAS and KRAS isoforms are almost identical proteins that are ubiquitously expressed and activate a common set of effectors. In vivo studies have revealed that they are not biologically redundant; however, the isoform-specificity of Ras signaling remains poorly understood. Using a novel panel of isogenic SW48 cell lines endogenously expressing wild type or G12V mutated activated Ras isoforms we have performed a detailed characterization of endogenous isoform-specific mutant Ras signaling. We find that despite displaying significant Ras activation, the downstream outputs of oncogenic Ras mutants are minimal in the absence of growth factor inputs...
February 20, 2019: Molecular Biology of the Cell
https://read.qxmd.com/read/30785850/the-relationship-between-metastatic-potential-and-in-vitro-mechanical-properties-of-osteosarcoma-cells
#15
Claude N Holenstein, Aron Horvath, Barbara Schär, Angelina D Schoenenberger, Maja Bollhalder, Nils Goedecke, Guido Bartalena, Oliver Otto, Maik Herbig, Jochen Guck, Daniel A Müller, Jess G Snedeker, Unai Silvan
Osteosarcoma is the most frequent primary tumor of bone and is characterized by its high tendency to metastasize in lungs. Although in case of being early diagnosed treatment results in a 5-year survival rate of nearly 60%, prognosis of patients with secondary lesions at diagnosis is poor and their 5-year survival rate remains below 30%. In the present work we have used a number of analytical methods to investigate the impact of increased metastatic potential on the biophysical properties and force generation of osteosarcoma cells...
February 20, 2019: Molecular Biology of the Cell
https://read.qxmd.com/read/30785847/choice-between-1-and-2-furrow-cytokinesis-in-caenorhabditis-elegans-embryos-with-tripolar-spindles
#16
Tomo Kondo, Akatsuki Kimura
Excessive centrosomes often lead to multipolar spindles, and thus probably to multipolar mitosis and aneuploidy. In Caenorhabditis elegans, approximately 70% of the paternal emb-27APC6 mutant embryonic cells contained more than two centrosomes and formed multipolar spindles. However, only 30% of the cells with tripolar spindles formed two cytokinetic furrows. The rest formed one furrow, similar to normal cells. To investigate the mechanism via which cells avoid forming two cytokinetic furrows even with a tripolar spindle, we conducted live-cell imaging in emb-27APC6 mutant cells...
February 20, 2019: Molecular Biology of the Cell
https://read.qxmd.com/read/30785846/myosin-iia-drives-membrane-bleb-retraction
#17
Nilay Taneja, Dylan T Burnette
Membrane blebs are specialized cellular protrusions that play diverse roles in processes such as cell division and cell migration. Blebbing can be divided into three distinct phases- bleb nucleation, bleb growth and bleb retraction. Following nucleation and bleb growth, the actin cortex, comprising actin, cross-linking proteins and non-muscle myosin II (MII), begins to re-assemble on the membrane. MII then drives the final phase, bleb retraction, which results in re-integration of the bleb into the cellular cortex...
February 20, 2019: Molecular Biology of the Cell
https://read.qxmd.com/read/30785842/cellular-crowding-influences-extrusion-and-proliferation-to-facilitate-epithelial-tissue-repair
#18
Jovany Franco, Youmna Atieh, Chase D Bryan, Kristen M Kwan, George T Eisenhoffer
Epithelial wound healing requires a complex orchestration of cellular rearrangements and movements to restore tissue architecture and function after injury. While it is well-known that mechanical forces can affect tissue morphogenesis and patterning, how the biophysical cues generated after injury influence cellular behaviors during tissue repair is not well understood. Using time-lapse confocal imaging of epithelial tissues in living zebrafish larvae, we provide evidence that localized increases in cellular crowding during wound closure promote the extrusion of non-apoptotic cells via mechanically regulated stretch-activated ion channels (SACs)...
February 20, 2019: Molecular Biology of the Cell
https://read.qxmd.com/read/30785840/the-putative-g-protein-coupled-receptor-grld-mediates-extracellular-polyphosphate-sensing-in-dictyostelium-discoideum
#19
Patrick M Suess, Yu Tang, Richard H Gomer
Five or more orthophosphates bound together by high energy phospho-anhydride bonds are highly ubiquitous inorganic molecules called polyphosphate. Polyphosphate acts as a signaling molecule eliciting a number of responses in eukaryotic cells, but the mechanisms mediating these effects are poorly understood. Proliferating Dictyostelium discoideum cells accumulate extracellular polyphosphate. At extracellular concentrations similar to those observed in stationary phase cells, polyphosphate inhibits proteasome activity and proliferation, and induces aggregation...
February 20, 2019: Molecular Biology of the Cell
https://read.qxmd.com/read/30785839/mps1-regulates-spindle-morphology-through-mcrs1-to-promote-chromosome-alignment
#20
Hongdan Yang, Fengxia Zhang, Ching-Jung Huang, Jun Liao, Ying Han, Piliang Hao, Youjun Chu, Xiaoai Lu, Wenshu Li, Hongtao Yu, Jungseog Kang
Accurate partitioning of chromosomes during mitosis is essential for genetic stability and requires the assembly of the dynamic mitotic spindle and proper kinetochore-microtubule attachment. The spindle assembly checkpoint (SAC) monitors the incompleteness and errors in kinetochore-microtubule attachment and delays anaphase. The SAC kinase Mps1 regulates the recruitment of downstream effectors to unattached kinetochores. Mps1 also actively promotes chromosome alignment during metaphase, but the underlying mechanism is not completely understood...
February 20, 2019: Molecular Biology of the Cell
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