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PubMed Journal Database | Molecular biology of the cell RSS

02:15 EDT 22nd March 2019 | BioPortfolio

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Showing PubMed Articles 1–25 of 235 from Molecular biology of the cell

In vitro BioID: Mapping the CENP-A Micro-Environment with high temporal and spatial resolution.

The centromere is located at the primary constriction of condensed chromosomes where it acts as a platform regulating chromosome segregation. The histone H3 variant CENP-A is the foundation for kinetochore formation. CENP-A directs formation of a highly dynamic molecular neighbourhood whose temporal characterisation during mitosis remains a challenge due to limitations in available techniques. BioID is a method that exploits a "promiscuous" biotin ligase (BirA118R or BirA*) to identify proteins within close...

Drosophila p53 directs non-apoptotic programs in postmitotic tissue.

TP53 is the most frequently mutated gene in human cancers, and despite intensive research efforts, genome-scale studies of p53 function in whole animal models are rare. The need for such in vivo studies is underscored by recent challenges to established paradigms, indicating that unappreciated p53 functions contribute to cancer prevention. Here we leveraged the Drosophila system to interrogate p53 function in a postmitotic context. In the developing embryo, p53 robustly activates important apoptotic genes i...

A specialized condensin complex participates in somatic nuclear maturation in Tetrahymena thermophila.

Condensins are highly conserved proteins that are important for chromosome maintenance in nearly all forms of life. While many organisms employ two forms of the condensin complex, the condensin genes in Tetrahymena have expanded even further. Here we report a form of condensin that is specifically active during sexual reproduction. This complex, condensin D, is composed of the core condensin proteins, Smc2 and Smc4, and two unique subunits, the kleisin Cph5 and Cpd2. Cpd2 is also found in somatic nuclei in ...

Hic-5 regulates Src-induced invadopodia rosette formation and organization.

Fibroblasts transformed by the proto-oncogene Src form individual invadopodia that can spontaneously self-organize into large matrix-degrading super-structures called rosettes. However, the mechanisms by which the invadopodia can spatio-temporally reorganize their architecture is not well understood. Herein, we show that Hic-5, a close relative of the scaffold protein paxillin, is essential for the formation and organization of rosettes in active Src-transfected NIH3T3 fibroblasts and cancer-associated fibr...

IRSp53 coordinates AMPK and 14-3-3 signaling to regulate filopodia dynamics and directed cell migration.

Filopodia are actin-filled membrane protrusions that play essential roles in cell motility, cell-cell communication, and act as precursors of dendritic spines. IRSp53 is an essential regulator of filopodia formation, which couples Rho-GTPase signaling to actin cytoskeleton and membrane remodeling. IRSp53 has three major domains: an N-terminal inverse-BAR (I-BAR) domain, a Cdc42- and SH3-binding CRIB-PR domain, and an SH3 domain that binds downstream cytoskeletal effectors. Phosphorylation sites in the regio...

Mitochondrial carrier protein overloading and misfolding induce aggresomes and proteostatic adaptations in the cytosol.

Studies in yeast showed that mitochondrial stressors not directly targeting the protein import machinery can cause mitochondrial Precursor Overaccumulation Stress (mPOS) in the cytosol independent of bioenergetics. Here, we demonstrate mPOS and stress responses in human cells. We show that overloading of mitochondrial membrane carriers, but not matrix proteins, is sufficient to induce cytosolic aggresomes and apoptosis. The aggresomes appear to triage unimported mitochondrial proteins. Interestingly, expres...

Correction.

Motors in transport and cytoskeleton remodeling.

Desiccation tolerance: an unusual window into stress biology.

Climate change has accentuated the importance of understanding how organisms respond to stresses imposed by changes to their environment, like water availability. Unusual organisms, called anhydrobiotes, can survive loss of almost all intracellular water. Desiccation tolerance of anhydrobiotes provides an unusual window to study the stresses and stress response imposed by water loss. Because of the myriad of stresses that could be induced by water loss, desiccation tolerance seemed likely to require many es...

Cell cycle, cell division, cell death.

Organelle zones.

The role of metabolism in cellular processes.

Spindle mechanics and chromosome segregation.

TgCep250 is dynamically processed through the division cycle and essential for structural integrity of the Toxoplasma centrosome.

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 thei...

ELMOD2 regulates mitochondrial fusion in a mitofusin-dependent manner, downstream of ARL2.

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 th...

Myosin II governs intracellular pressure and traction by distinct tropomyosin-dependent mechanisms.

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 i...

Stretching magnitude-dependent inactivation of AKT by ROS led to enhanced p53 mitochondrial translocation and myoblasts apoptosis.

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 inactiva...

Integrin α6β4E variant is associated with actin and CD9 structures and modifies the biophysical properties of cell-cell and cell-ECM interactions.

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 epithe...

Retromer facilitates the localization of Bcl-xL to the mitochondrial outer membrane.

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...

Nestin in immature embryonic neurons affects axon growth cone morphology and Semaphorin3a sensitivity.

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 ...

PP2A-B55/SUR-6 collaborates with the nuclear lamina for centrosome separation during mitotic entry.

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. Mechan...

Lymphatic endothelial cell calcium pulses are sensitive to spatial gradients in wall shear stress.

Cytosolic calcium (Ca) is a ubiquitous second messenger that influences numerous aspects of cellular function. In many cell types cytosolic Ca concentrations are characterized by periodic pulses whose dynamics can influence downstream signal transduction. Here, we examined the general question of how cells use Ca 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 Ca dynamics in LECs, and that Ca-dep...

CEP135 isoform dysregulation promotes centrosome amplification in breast cancer cells.

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 f...

Regulation of LC3 Lipidation by the Autophagy-Specific Class III Phosphatidylinostitol-3 Kinase Complex.

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 comp...

Syntaxin 11 regulates the stimulus-dependent transport of Toll-like receptor 4 to the plasma membrane by cooperating with SNAP-23 in macrophages.

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 h...


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