JCB

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 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 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 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 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.

 

New issue: December 10th

In today’s new issue of JCB, Cheadle and Biederer identify a postsynaptic signaling protein called Farp1 that works with the synaptic adhesion molecule SynCAM1 to organize both sides of neuronal synapses. As explained in this week’s In Focus, Farp1 promotes the assembly of postsynaptic dendritic spines, but also organizes presynaptic active zones, leading senior author, Thomas Biederer to stress that “when we look at synapses, we should think of them as a structural and functional unit.”

Staying with neurobiology, Van de Bospoort et al. describe how Munc13 proteins control when and where dense-core vesicles (DCVs) are released from neurons. Munc13 proteins are absolutely required for the release of neurotransmitter-containing synaptic vesicles, but Van de Bospoort et al. find that neuropeptide-contanining dense-core vesicles are still released in the absence of Munc13 family members. However, Munc13 proteins boost the efficiency of dense-core vesicle fusion at pre-synaptic terminals, so that their contents are preferentially released from synapses instead of other parts of the neuron. More here.

Elsewhere, Trueman et al. identify a “gating motif” in the Sec61 translocon, that helps determine whether or not the channel opens up to allow proteins pass through it into the endoplasmic reticulum. As explained here, the researchers create several point mutations in budding yeast Sec61 that either boost or restrict the channel’s activity. The critical residues appear to open up the Sec61 channel to proteins with sufficiently hydrophobic signal sequences.

Ricke et al. reveal that mice expressing an inactive version of the mitotic checkpoint kinase Bub1 aren’t susceptible to cancer, even though they frequently mis-segregate their chromosomes. As described in this summary, mice expressing a kinase-dead Bub1 mutant fail to recruit the error-correcting kinase Aurora B to centromeres, leading to incorrect attachments between kinetochores and the mitotic spindle. Despite a high rate of chromosome mis-segregation and aneuploidy, however, the mice are no more prone to cancer than wild-type animals, suggesting that Bub1’s kinase activity is somehow required for tumorigenesis.

Nevertheless, abnormal mitoses are largely thought to contribute to tumorigenesis by causing chromosome mis-segregation and aneuploidy. But Ganem and Pellman provide a review in today’s JCB explaining that problems in mitosis can also lead to DNA damage and mutations. Author Neil Ganem explains how DNA damage can arise during mitosis in this month’s biobytes podcast, where you can also hear Anne Royou discuss her lab’s recent study (Kotadia et al.) exploring how cells try to avoid mitotic errors by coordinating chromosome segregation with cytokinesis. You can listen below or subscribe in iTunes.

That’s all for now, but make sure to examine the full list of papers in today’s new issue by reading the table of contents here.

Cover image © 2012 Cheadle and Biederer. 

 

New issue: November 12th

In today’s new issue, Reymond et al. describe how the Rho family GTPase Cdc42 helps metastasizing cancer cells move out of the bloodstream to colonize new tissues. The researchers find that Cdc42 promotes the expression of the adhesion receptor β1-integrin, which allows cancer cells to attach to endothelial cells and their underlying extracellular matrix, facilitating their migration across the endothelial barrier. As explained in this week’s In Focus, inhibiting this process by transiently depleting Cdc42 is sufficient to reduce the formation of metastases in vivo.

TerBush and Osteryoung examine the different contributions of two cytoskeletal proteins to chloroplast division. Together, the tubulin-like GTPases FtsZ1 and FtsZ2 form a Z-ring at the equator of chloroplasts that helps the organelle divide in two. By expressing the proteins in fission yeast, TerBush and Osteryoung suggest that FtsZ2 mainly dictates the Z-ring’s shape, whereas FtsZ1 determines the structure’s dynamics. More here. And staying with organelle division, Bui et al. describe how the dynamin-related protein Dnm1 is recruited to the outer membrane of yeast mitochondria in order to drive mitochondrial fission. You can learn more in this summary.

Li et al. reveal that the ARL13B GTPase, which is mutated in the human ciliopathy Joubert Syndrome, must be conjugated to the small, ubiquitin-like modifier SUMO to promote the targeting of sensory receptors into the primary cilium. Cells expressing a non-SUMOylatable version of the GTPase still form cilia, but several receptors fail to localize to the ciliary membrane, disrupting various signaling pathways. Senior author Jinghua Hu explains here how this might explain some of the symptoms suffered by Joubert syndrome patients.

And Raab et al. describe the distinct contributions of myosin IIA and myosin IIB to durotaxis, the phenomenon in which cells migrate from softer to stiffer matrices. Senior author Dennis Discher discusses his lab’s results in this month’s biobytes podcast, where you can also hear Ivan Nabi describe his recent study (Joshi et al.) revealing that caveolin-1 acts as mechanotransducer to increase the assembly of plasma membrane caveolae to help cells cope with mechanical stress. You can listen below, or subscribe in iTunes.

There are lots of other interesting papers in today’s new issue – you can find them all on our table of contents here – but, finally for today, I’ll point you in the direction of the latest in our series of features on Cell Biology and Biomedicine. Oliver Hantschel and Giulio Superti-Furga describe how basic cell biological research is now one of the key drivers for therapeutic innovations, Larry Goldstein discusses the therapeutic potential of pluripotent stem cells, and Alfred Goldberg details the development of proteasomal inhibitors as anti-cancer agents.

Cover image © 2012 Reymond et al.

New issue: October 15th

In today’s new issue, Yoo et al. reveal how transient signaling events induced immediately upon wounding are required for the subsequent regeneration of zebrafish fins. In particular, reactive oxygen species rapidly activate the Src family kinase Fyn in injured epithelia, and blocking this activation inhibits the regrowth of wounded fins three days later. And, as you can read in this week’s In Focus, intracellular calcium release and activation of the MAP kinase ERK are also critical events in setting up the regeneration process.

Keller et al. describe how two membrane transport pathways cooperate to integrate a bacterial redox protein into the plasma membrane. The Sec pathway inserts the first two transmembrane domains of the S. coelicolor Rieske protein into the membrane, but the twin-arginine transport, or Tat, pathway takes over to integrate the third transmembrane domain and translocate the protein’s C-terminal iron-sulphur domain across the plasma membrane. More here.

Lapointe et al. reveal how the partial depletion of a mitochondrial enzyme inhibits respiration. The mitochondrial hydroxylase MCLK1 helps to synthesize the coenzyme ubiquinone (also known as coenzyme Q), which transfers electrons along the respiratory chain of the mitochondrial inner membrane. Mice with a single copy of the Mclk1 gene show reduced mitochondrial respiration, even though their ubiquinone levels appear to be unchanged. Lapointe et al. find that ubiquinone’s distribution is altered in Mclk1 heterozygotes, so that the coenzyme is less abundant in the mitochondrial inner membrane while its levels increase in the outer membrane. The disruption to mitochondrial respiration and metabolism may explain why Mclk1 heterozygotes have a longer lifespan than wild-type animals. You can read a slightly longer summary here.

Wang et al. describe how integrin-based cell-matrix adhesions activate the Rac GTPase to control adhesion turnover and cell migration (summary here) while Nanes et al. reveal that p120-catenin regulates the turnover of cadherin-based cell-cell adhesion by masking an endocytic signal in the cytoplasmic tail domain of cadherins. You can learn more about this latter story by reading the comment article by Mirna Perez-Moreno and Elaine Fuchs, and you can also hear the paper’s senior author Andrew Kowalczyk discuss his lab’s results in this month’s biobytes podcast. You can subscribe in iTunes or listen below, where you’ll also hear Mark Ginsberg and colleagues describe their recent study of how KRIT1 – a protein linked to cerebral cavernous malformations – localizes to endothelial cell-cell junctions to regulate cardiovascular development.

Finally for today, I’ll point you in the direction of the latest three articles in our series of features on cell biology and biomedicine. This week, Atwood et al. discuss the use of Hedgehog pathway inhibitors to treat various tumors, Okiyoneda and Lukacs discuss ways to treat cystic fibrosis, and Houtkooper and Auwerx describe the therapeutic potential of NAD+.

Lots of other interesting papers in today’s new issue as well. As always, you can find them listed on our table of contents by clicking here.

Cover image © 2012 Yoo et al.

New issue: September 17th

Just time for a quick roundup of some of the highlights from today’s new issue. Mall et al. report that the disassembly of the nuclear lamina during mitosis is initiated by lipin enzymes, which generate the lipid diacylglycerol in order to activate Protein kinase C and trigger nuclear lamin phosphorylation. More here.

Chartier et al. reveal that the apical membrane protein Crumbs protects Drosophila photoreceptor cells from light-induced degeneration by limiting the production of reactive oxygen species by Rac1 and the enzyme NADPH Oxidase. The results may explain why mutations in human Crumbs cause retinal dystrophies and blindness. You can read more in this summary.

Lemieux et al. describe how microtubules help calcium calmodulin-dependent kinase II localize to dendritic sites where it can remodel synapses in response to local increases in calcium levels (more here). Kashikar et al., on the other hand, examine how sperm decipher the complex calcium signals they receive as they navigate toward the egg, revealing how they sample their surroundings at regular intervals and adjust their sensitivity as they draw nearer to their target. Mitch Leslie provides more details in this week’s In Focus.

Finally for today, Rodríguez-Fraticelli et al. demonstrate that physically confining epithelial cells limits their ability to spread, thereby promoting polarization and the formation of an apical lumen. You can hear senior author Fernando Martín-Belmonte describe his group’s findings in this month’s biobytes podcast, where you can also hear Fabien Le Grand discuss his recent paper exploring how the transcription factor Six1 regulates muscle regeneration and stem cell self-renewal. You can listen below or subscribe in iTunes.

Unfortunately, I didn’t have time to describe all the interesting papers you can find in today’s new issue. You can see them for yourself on our table of contents by clicking here.

Cover image courtesy of Francois Chartier.

 

New issue: July 23rd

In today’s new issue of JCB, Garbett and Bretscher reveal that a scaffold protein required to hold membrane proteins inside microvilli is surprisingly dynamic. EBP50 promotes microvillar assembly by linking the actin-binding protein ezrin to several plasma membrane proteins. But Garbett and Bretscher show that EBP50 turns over much more rapidly in microvilli than its binding-partners do, a behavior promoted by the protein’s PDZ domains and a still-to-be-identified binding partner. More here.

Wurzenberger et al. identify two phosphatase-targeting proteins that help to counteract the Aurora B kinase in anaphase cells in order to promote accurate chromosome segregation. In early mitosis, Aurora B destabilizes incorrect kinetochore-microtubule attachments that aren’t under tension. But when sister chromatids separate at the beginning of anaphase, the tension on all kinetochores decreases, so Aurora B activity must be restricted for spindle microtubules to successfully pull the chromatids to opposite spindle poles. Wurzenberger et al. reveal that Sds22 and Repo-Man recruit Protein Phosphatase 1 to anaphase chromosomes, preventing Aurora B from destabilizing their microtubule tachments. In the absence of these phosphatase subunits, chromosomes frequently mis-segregate as their attachments to the spindle are disrupted. Further details here.

Meanwhile, Guo et al. describe how the mitotic kinase BubR1 phosphorylates itself in order to promote accurate chrtomosome segregation. As described here, the researchers found that blocking BubR1 autophosphorylation both weakens the mitotic checkpoint and decreases Aurora B’s ability to eliminate incorrect kinetochore-microtubule attachments in early mitosis.

van Gisbergen et al. describe how the phospholipid PI(3,5)P2 targets formin proteins to the cortex of plant cells, where they assemble actin filaments to promote polarized growth. As described in this week’s In Focus, the class II formins For2A and B are targeted to dynamic membrane patches in moss cells by their N-terminal phospholipid-binding domain, which is highly homologous to the lipid phosphatase PTEN.

And finally for today, Yamamoto et al. identify a population of vesicles that provide membrane for the formation of the autophagosome, the organelle that engulfs cytoplasmic contents and delivers them to lysosomes for degradation during autophagy. Fulvio Reggiori and Sharon Tooze provide a comment on the study, and you can hear the paper’s senior author Yoshinori Ohsumi describe his lab’s results in this month’s biobytes podcast. You can subscribe in iTunes or listen below, where you’ll also hear Shaohua Li discuss his lab’s recent paper describing how hypoxia and the pro-apoptotic proteins Bnip3 and AIF help hollow out the center of developing epithelial tissues.

There are lots more interesting papers to discover in today’s new issue. You can find them all listed on our table of contents by clicking here.

Cover image © 2012 Garbett and Bretscher.