JCB

New issue: May 13th 2013

Time for a quick roundup of some of the highlights from today's new issue of JCB...

Kleiblova et al. identify mutations in the phosphatase Wip1 that enable cancer cells to foil the tumor suppressor p53. As explained in this week's In Focus, the mutations generate truncated versions of Wip1 that are more stable than the wild-type protein, and are therefore better able to inactivate p53 and permit cells to override the DNA damage checkpoint.

Snow et al. reveal that Progerin, a mutant form of lamin A expressed in Hutchinson-Gilford Progeria syndrome, disrupts the import of large protein cargoes into the nucleus by lowering the levels of nuclear RanGTPase. More here.

Civelekoglu-Scholey et al. model the dynamics of metaphase chromosomes in Ptk1 cells. As explained here, Ptk1 cells represent in unusual case in which chromosomes at the edge of the metaphase plate are immobile, whereas the ones in the central region oscillate. Civelekoglu-Scholey et al. reveal that these different behaviors are due to regional differences in the strength of the polar ejection forces that push chromosomes toward the cell equator.

And Graziano et al. report a new mechanism for controlling actin nucleation, identifying a budding yeast protein, Bil1, that activates the nucleation promoting factor Bud6, which, in turn, stimulates the formin Bnr1 to initiate actin cable assembly. As described in this summary, this is an unusual way of regulating actin assembly, as nucleation tends to be initiated by proteins working in pairs, rather than in groups of three.

And, finally for today, this month’sbiosights video podcast features Roberta Martinelli and Christopher Carman, who discuss their recent paper describing how a loss of tension inside endothelial cells induces the formation of ventral membrane protrusions that close the holes left by transmigrating leukocytes. You can watch it here or subscribe in iTunes and, if you'd like to discuss Martinelli et al.'s findings with your lab, you can download a “Journal Club Pack” – including a pdf of the paper and a PowerPoint file of their figures – by clicking here.

That's all for today, but you can find the full table of contents for today's new issue by clicking here.

Cover image of nuclear import in the presence and absence of progerin © 2013 Snow et al.

New issue: April 29th 2013

In today’s new issue of JCB, Sugiyama et al. reveal that the matrix metalloprotease MT1 regulates cancer cell invasion by cleaving the receptor tyrosine kinase EphA2. The cleavage, and subsequent internalization of EphA2 initiates a Rho-dependent signaling pathway that prompts cells to roundup and detach from their neighbors, promoting their ability to disseminate from tumors as individual cells instead of invading as a cell collective. More here.

Morais da Silva et al. reveal that the spindle checkpoint protein Bub3 suppresses tumor development independently of its role in chromosome segregation. Fly cells lacking Bub3 hyperproliferate and form tumors as long as they’re prevented from undergoing apoptosis. But cells in which Bub3 is merely displaced from kinetochores – inhibiting the spindle assembly checkpoint and inducing chromosome mis-segregation – don’t form tumors. As explained here, this suggests that cytoplasmic Bub3 has an additional function that limits cell proliferation.

Upadhyay et al. describe how a protein called Sanpodo regulates the fate of fly sensory organ precursor cells. Sanpodo boosts Notch signaling in some precursor cells by binding to the γ-secretase complex that cleaves and activates the Notch receptor. In other progenitors, however, Sanpodo suppresses Notch signaling by removing the receptor from the plasma membrane. You can learn more in this week’s In Focus.

Elsewhere, Zhong et al. reveal how an excess of replication forks can slow the rate of DNA synthesis, whereas reduced replication origin firing leads to faster rates of replication. As explained in this summary, this suggests that individual forks compete for essential replication factors and nucleotides. And Bergoglio et al. describe how DNA polymerase η helps replicate problematic regions of the genome, thereby preventing chromosomal rearrangements that can drive tumorigenesis. You can learn more about this paper by listening to this month’s biobytes podcast, which features an interview with the study’s senior author Jean-Sébastien Hoffmann. You can also hear Julie Donaldson discuss her lab’s recent paper (Maldonado-Báez et al.) describing how cells rapidly sort and recycle membrane proteins internalized by clathrin-independent endocytosis.

That’s all for today, but you can find the full list of today’s new papers by visiting our table of contents here.

Cover image of a Drosophila pupa expressing a GFP fusion protein in its peripheral nervous system © 2013 Upadhyay et al.

New issue: April 15th 2013

Time for a roundup of some of the highlights from today’s new issue of JCB…

Ching et al. develop an unbiased method to identify genomic loci that interact with nuclear particles called PML bodies. The researchers use an anti-PML antibody to direct the biotinylation of chromatin in close proximity to PML bodies, allowing these loci to be isolated and characterized. By using different antibodies, the technique can easily be adapted to identify genomic loci associated with other subnuclear structures, such as the nuclear lamina or DNA repair foci. You can read more about the method, and what Ching et al.’s results suggest about the function of PML bodies, in this week’s In Focus.

Elsewhere, Lechtreck et al. describe how a protein complex linked to human disease helps export signaling proteins out of cilia. As described in this summary, the BBSome, a complex of 7 proteins mutated in Bardet-Biedl syndrome, works with intraflagellar transport particles to remove the signaling enzyme phospholipase D from the cilia of green algae, perhaps by acting as a cargo adaptor.

Díaz et al. reveal how several signaling pathways combine to enhance cancer cell invasion. The researchers find that hypoxia promotes the formation of invasive membrane protrusions called invadopodia by activating the Notch signaling pathway. Notch, in turn, induces the ADAM12 metalloprotease to cleave and release the HB-EGF growth factor from the surface of cancer cells. HB-EGF then activates the EGF receptor to promote invadopodia formation, potentially in distant tumor cells that are not themselves experiencing hypoxia. As discussed here, this could allow tumor cells to coordinate their collective invasion of surrounding tissues.

And Shao et al. report the surprising finding that Xenopus oocytes lack the spindle assembly checkpoint, which normally prevents cells from dividing with misaligned chromosomes, and can therefore undergo meiosis in the absence of microtubules or in the presence of monopolar spindles. You can read more in this summary, or you can listen to senior author Johné Liu discuss his lab’s findings in this month’s biosights video podcast.

If you’d like to discuss Shao et al.’s study with your colleagues, you can download a “Journal Club Pack” – including a pdf of the paper and a PowerPoint file of their figures – by clicking here.

That’s all for today, but don’t forget to check out all the papers in today’s new issue by visiting our table of contents here.

Cover image, showing Chlamydomonas zygotes in which phospholipase D (red) has been exported from cilia (green) by the BBSome, © 2013 Lechtreck et al.

New issue: April 1st 2013

In today’s new issue of JCB, Gascoigne and Cheeseman investigate how cells regulate the assembly and disassembly of kinetochores at the beginning and end of mitosis. As described in this week’s In Focus, the researchers find that these multiprotein complexes, which connect chromosomes to spindle microtubules, are regulated by cyclin-dependent kinases and by the exclusion of key components from the nucleus. When Gascoigne and Cheeseman prevent kinetochores from disassembling at the end of mitosis, cells have problems segregating their chromosomes in subsequent rounds of division.

Shrimal et al. describe how cells use a specific isoform of the enzyme oligosaccharyltransferase (OST) to glycosylate proteins at C-terminal sites. The catalytic subunit of OST comes in two different isoforms, STT3A and STT3B. STT3A associates with protein translocation channels in the ER membrane and N-glycosylates most of a nascent protein’s glycosylation sites as it enters the ER lumen. But, as explained here, glycosylation sites near the C-terminus of proteins aren’t exposed to STT3A until translation has finished. Shrimal et al. find that STT3B is responsible for glycosylating these sites, after the protein has been completely translocated into the ER.

Elsewhere, Hong et al. reveal how the binding of actin filaments to cadherin adhesion molecules helps stabilize cadherin clusters during the assembly of intercellular adherens junctions. You can read more in this summary. And Schwab et al. show that, by allowing cells to efficiently replicate difficult-to-copy regions of their genomes, the DNA helicase FANCJ also helps cells maintain chromatin organization, preventing the spread of inactive, heterochromatin domains. More here.

Meanwhile, Reboutier et al. take a chemical genetics approach to demonstrate that the Aurora A kinase – best known for its critical functions in early mitosis – also has an important role later in cell division, when it promotes assembly of the central spindle during mitosis. You can listen to authors David Reboutier and Claude Prigent discuss their findings in this month’s biobytes podcast, where you can also hear Ingrid Hoffman describe her lab’s recent finding (Zhu et al.) that the actin-binding protein MISP helps orient the mitotic spindle downstream of the kinase Plk1. You can listen to the podcast below or subscribe in iTunes.

That’s all for today, but there are plenty of other interesting paper’s in today’s new issue. You can explore them all by visiting our table of contents here.

 

Cover image of cells expressing a mutant version of E-cadherin fused to the actin-binding domain of alpha-catenin (green) and stained for F-actin (red) © 2013 Hong et al.

New issue: March 18th 2013

In today’s new issue of JCB, Breker et al. catalog how the abundance and localization of every yeast protein changes in response to different environmental stresses. Each stress induces a unique “thumbprint” of proteomic changes, many of which can’t be explained by differences in gene transcription. The subcellular localization of proteins is much more dynamic than expected and, as explained in this week’s In Focus, the researchers identify specific “bet-hedging” strategies that yeast use to survive adverse conditions.

Neelsen et al. describe how certain oncogenes can perturb DNA replication and induce DNA damage. By pushing cells into S phase prematurely, the oncogenes Cyclin E and Cdc25A induce the formation of “reversed replication forks”, in which newly-synthesized DNA strands anneal to each other instead of their parental strands. As discussed here, if these unusual replication intermediates aren’t resolved before mitosis, a mitotic nuclease called Mus81 can cleave them and generate DNA double strand breaks.

Meanwhile, Zou et al. reveal how DNA replication is promoted by a protein linked to mental retardation. CUL4B is a member of the cullin family of ubiquitin ligase scaffold proteins. As described here, Zou et al. find that CUL4B inhibits the production of two microRNAs that target the cyclin-dependent kinase CDK2. In the absence of CUL4B, CDK2 levels are reduced, which, in turn, leads to a decrease in the amount of CDC6, a key “licensing factor” that helps initiate DNA replication.

Lewellyn et al. describe how a protein kinase called Misshapen regulates cell migration to shape Drosophila egg chambers. Misshapen promotes the migration of egg chamber follicle cells by reducing the levels of integrin adhesion receptors at the basal surface. The coordinated movement of the follicle cells rotates the egg chambers, helping them elongate from a spherical to an oval shape. More here.

Finally for today, we turn to mouse oocytes instead of fly eggs for this month’s biosights video podcast. In the video below, Rong Li discusses her lab’s recent paper (Yi et al.) describing how the actin nucleators Formin2 and the Arp2/3 complex help push chromosomes to the periphery of mammalian oocytes during meiosis, in preparation for asymmetric cell division.

If you’d like to discuss Yi et al.’s study with your colleagues, you can download a “Journal Club Pack” – including a pdf of the paper and a PowerPoint file of their figures – by clicking here.

And, of course, if you’d like to discuss any of today’s new JCB papers with your colleagues, you can find them all listed on our table of contents here.

Cover image, showing a Drosophila egg chamber in which GFP-negative cells lack the Misshapen kinase, © 2013 Lewellyn et al.

New issue: March 4th 2013

In today’s new issue of JCB, Ellis et al. describe the origin and function of notochord vacuoles, large, membrane-bound organelles that form in the inner cells of the notochord during embryogenesis. These compartments been recognized for a long time, but their identity and function during development has remained mysterious. But, as described in this week’s In Focus, Ellis et al. reveal that these vacuoles are lysosome-related organelles that function in both embryonic axis elongation and spine morphogenesis in zebrafish.

Ingerman et al. reveal how ATP hydrolysis by the Arp2/3 complex promotes the disassembly of lamellipodial actin networks. By making hydrolysis-defective mutants of the actin-related subunits Arp2 and Arp3, Ingerman et al. show that ATP hydrolysis isn’t required for the complex to assemble branched actin networks. But these network sturnover more slowly when ATP hydrolysis is inhibited. More here.

Yagita et al. describe how an integral membrane protein is delivered directly to mammalian peroxisomes. As described in this summary, PEX26 is a tail-anchored peroxisomal membrane protein that contains a single transmembrane domain at its C-terminus. Unlike its budding yeast ortholog, which is inserted into the ER before being translocated to peroxisomes, mammalian PEX26 is bound in the cytosol by the chaperone PEX19, which then delivers the protein to peroxisomes by binding to a peroxisomal receptor called PEX3.

And Rohner et al. describe how the heat shock gene hsp16.2 associates with nuclear pore complexes in C. elegans cells. The researchers find that the stress response gene localizes near the nuclear periphery in its inactive state, and becomes strongly associated with nuclear pores when induced by heat shock. This association is mediated by the gene’s promoter region and several factors that bind to it, including heat shock transcription factor 1 and RNA polymerase II. Senior author Susan Gasser explains here how this localization might aid the heat shock gene’s function.

You can find all of today’s new papers listed here, but I’ll leave you for today with a link to our latest biobytes podcast, in which you can hear Sachiyo Kawamoto describe her recent study (Kim et al.) of how an RNA-binding protein promotes neuronal differentiation, and Rosa Puertollano describes her paper (Martin and Puertollano) exploring the regulation of TFEB, a transcription factor that promotes autophagy and lysosome biogenesis. You can listen below or subscribe in iTunes.

Cover image, showing the vacuoles (red) found in zebrafish notochord cells (labeled with the membrane marker GFP-CaaX), © 2013 Ellis et al.

New issue: February 18th 2013

In today’s new issue of JCB, Jose et al. use mathematical modeling and cell imaging to demonstrate how endoyctosis and exocytosis cooperate to polarize budding yeast. The researchers show that endocytosis promotes cell polarization by limiting – or “corralling” – the region where exocytic vesicles containing the polarity protein Cdc42 are delivered to the cell surface. You can read more in this week’s In Focus.

Elsewhere, Yoshida et al. identify a new type of microtubule organizing center in meiotic fission yeast. γ-tubulin-containing structures, which the researchers call “telocentrosomes”, help cluster telomeres and pair up homologous chromosomes during meiosis, in a process that involves both dynein and kinsein microtubule motors. More here.

Ono et al. reveal that the condensin II complex helps resolve sister chromatids during S phase. Both condensin I and condensin II compact mitotic chromosomes, but condensin II appears to function earlier in the cell cycle, helping to separate newly-synthesized chromatids from their sister in preparation for their subsequent segregation in mitosis. You can read more in this summary.

And Akopian et al. show that the bacterial protein channel SecYEG – the homolog of eukaryotic Sec61 – initiates handover of actively translating ribosomes. Instead of passively receiving ribosomes and nascent polypeptides from the signal recognition particle (SRP) and its membrane receptor FtsY, SecYEG induces a conformational change in SRP-FtsY that promotes ribosome transfer. Read more here.

There’s many more papers for you to discover – see the full table of contents here – but I’ll leave you for now with a link to this week’s biosights video podcast, in which Erfei Bi describes his recent paper (Wloka et al.) demonstrating that the budding yeast type II myosin Myo1 acts as an immobile scaffold at the bud neck to organize proteins involved in forming the primary septum during cytokinesis.

And don’t forget, if you’d like to discuss the implications of Wloka et al.’s study with your colleagues, you can download a “Journal Club Pack” – including a pdf of the paper and a PowerPoint file of their figures – by clicking here.

 

Cover image courtesy of Takao Ono.

New issue: February 4th 2013

In today’s new issue of JCB, Pettem et al. reveal that a neuronal protein linked to neurodevelopmental disorders suppresses the development of inhibitory synapses. MDGA1 disrupts the interaction between neuroligin-2 and neurexin-1, two synaptic cell adhesion molecules associated with autism and schizophrenia that promote inhibitory synapse development. MDGA family proteins have also been linked to autism and schizophrenia and, as explained in this week’s In Focus, Pettem et al.’s discovery could pave the way for treatments for both these disorders and for epilepsy.

Elsewhere, Blümer et al. demonstrate that Rab GTPases are targeted to the correct intracellular membrane by the guanine nucleotide exchange factors that activate them. The authors show that mislocalizing exchange factors to mitochondria membranes is sufficient to redirect their corresponding Rabs to mitochondria, explaining how different Rab proteins localize to specific intracellular compartments to regulate specific membrane trafficking events. More here.

Lewellis et al. describe how changes in a chemoattractant’s expression pattern guide migrating neurons to the right embryonic location. Zebrafish trigeminal sensory neurons are attracted by the chemokine SDF1a, whose expression is reduced in cells already passed by the neurons through the combined actions of a microRNA and the non-canonical chemokine receptor Cxcr7b. This maintains a relatively high concentration of SDF1a on one side of the migrating neurons, which helps steer them to the correct destination without them becoming distracted by alternative SDF1a sources. You can learn more in this summary.

Prota et al. describe how the enzyme tubulin tyrosine ligase (TTL) specifically recognizes the C-terminus of alpha-tubulin to modulate the behavior of microtubules. (Tyrosinated microtubules are more dynamic than detyrosinated ones). As described in this summary, the researchers obtain the crystal structure of TTL bound to alpha- and beta-tubulin heterodimers. The structure explains why TTL acts on dimers instead of polymerized microtubules, and why it tyrosinates the tail of alpha-, but not beta-tubulin.

Meanwhile, Sakamoto et al. describe how microtubules guide the reorganization of intermediate filaments in migrating astrocytes. Specifically, the researchers show that the tumor suppressor APC links microtubules to intermediate filaments in cell protrusions, a function that is critical for normal astrocyte migration. You can hear senior author Sandrine Etienne-Manneville discuss these findings in this month’s biobytes podcast, where you can also listen to Michael Lazarou describe his recent study into the function of PINK1 and Parkin – two mitochondrial proteins linked to Parkinson’s disease. You can listen below or subscribe in iTunes.

That’s all for today but, as always, you can find lots more interesting papers by visiting our table of contents.

Cover image © 2013 Pettem et al. 

New issue: January 21st 2013

Time for a quick roundup of some of the highlights from the latest issue of JCB…

Grotsky et al. describe how cancer cells overcome the loss of the tumor suppressor BRCA1. Cells lacking BRCA1 are unable to repair DNA double strand breaks by homologous recombination, rendering them vulnerable to cell senescence or apoptosis. But Grotsky et al. show that BRCA1-deificient cancer cells can resume homologous recombination and cell proliferation by upregulating a protease called cathepsin-L, which degrades an inhibitor of homologous recombination called 53BP1. You can learn more about this story, including why cathepsin-L might be useful as a diagnostic marker, in this week’s In Focus.

Cane et al. reveal that the chromokinesin NOD, a motor protein that pushes chromosomes away from spindle poles, stabilizes attachments between kinetochores and spindle microtubules. In addition, as described in this summary, the researchers demonstrate that NOD helps move chromosomes in two ways: by hauling them along microtubules and by attaching them to the tips of polymerizing filaments.

Staying with cell division, Hasegawa et al. clarify the role of RanGTP in the formation of mitotic spindles. In rapidly proliferating cells, a steep gradient of RanGTP forms around mitotic chromosomes, which helps to organize the surrounding spindle. Hasegawa et al. show that this RanGTP gradient is absent in slowly-proliferating fibroblasts. However, the gradient became steeper in fibroblasts forced to carry extra chromosomes, which may explain why aneuploid cancer cells divide more rapidly. More here.

Meanwhile, Kamimura et al. describe how the proteoglycan perlecan disperses Wnt proteins across the neuromuscular junction to regulate synapse development in Drosophila. As summarized here, in the absence of perlecan, presynaptic and postsynaptic differentiation is altered, as excess Wnt protein accumulates at the presynapse, while insufficient Wnt signaling occurs on the postsynaptic side.

And, finally, today also sees the release of the latest biosights video podcast, in which Maryna Kapustina discusses her recent paper describing how rapid cell shape changes, such as those involved in amoeboid-type cell migration, can be driven by the cyclic folding and unfolding of the plasma membrane and its underlying actin cortex. You can watch below and, if you’d like to discuss the implications of Kapustina et al.’s study with your colleagues, you can download a “Journal Club Pack” – including a pdf of the paper and a PowerPoint file of their figures.

That’s all for today but, as always, you can find plenty more interesting papers by visiting our table of contents here. 

Cover image courtesy of Tom Maresca.

New issue: January 7th, 2013

 

Today sees the release of the first JCB issue of the New Year. Here’s a quick guide to what you can find inside…

Leikina et al. identify several factors that regulate myoblast fusion, the process by which individual muscle precursor cells join together to form multinucleated myotubes. As explained in this week’s In Focus, the initial merger of individual cell membranes involves members of the annexin family of phospholipid-binding proteins, whereas later steps require the GTPase dynamin and the phospholipid PI(4,5)P₂.

Lee et al. describe how the ATPase ATAD5 promotes the disassembly of DNA replication factories (sites of active DNA synthesis), probably by removing the key replication factor PCNA from chromatin. In the absence of ATAD5, replication factories persist even after they’ve finished synthesizing DNA, decreasing the overall rate of DNA replication and slowing progression through S phase. You can learn more here.

Mohammadi and Isberg reveal that Cdc42 helps phagocytic cells internalize large particles by working with the exocyst complex to deliver membrane to the cell surface (more here), and Lampert et al. describe how two protein complexes combine to link kinetochores to spindle microtubules (summary here). Elsewhere, Hori et al. investigate how the kinetochore is assembled in an excellent paper discussed here by Ann Stankovic and Lars Jansen.

Today also sees the release of the latest biobytes pocast, which features two papers from the December 24^th issue of JCB that are well worth checking out if you missed them over the holidays. Didier Trouche describes how the p400 ATPase facilitates DNA repair (Courilleau et al.), and Veit Riechmann explains how the kinase Tao regulates epithelial cell shape changes (Gomez et al.). You can listen below or subscribe in iTunes.

That’s all for today, but you can find the full list of papers in today’s new issue by reading the table of contents here.