JCB biowrites

New issue: September 18th 2015

In the latest issue of JCB, Wynne and Funabiki reveal that, in the absence of microtubule attachments, a subset of kinetochore proteins form expanded structures that may help activate the spindle checkpoint and capture microtubules. As described in this week’s In Focus, treating Xenopus egg extracts with the microtubule-depolymerizing drug nocodazole causes multiple kinetochore proteins – including the spindle checkpoint regulators BubR1 and Mad1, as well as proteins, such as CENP-E and dynein, involved in lateral microtubule attachment – to form long, thin filaments that extend more than a micron away from the centromeres of mitotic chromosomes.

Kimura et al. describe how TRIM family proteins target specific inflammatory regulators for degradation via the autophagy pathway. As described here, TRIM20 targets several subunits of the inflammasome for degradation by linking them to key autophagy regulators such as ULK1 and Beclin1. TRIM21, on the other hand, links the transcription factor IRF3 – an activator of type I IFN responses – to the autophagy machinery.

Von Büdingen et al. reveal that a component of the myelin sheath surrounding spinal cord axons regulates the growth of neighboring unmyelinated neurons by sequestering NGF. NGF binds with high affinity to a myelin component called MOG, limiting its ability to stimulate the growth of unmyelinated pain-sensing neurons. MOG-deficient mice show increased sprouting of pain-sensing neurons, an observation that could help explain why patients suffering from the demyelinating disease multiple sclerosis often experience chronic neuropathic pain. More here.

Zhou et al. reveal that the disease-related protein progranulin gets a “piggyback” ride to lysosomes by binding to another lysosomal protein, prosaposin. Progranulin, which is mutated in both frontotemporal lobar degeneration and neuronal ceroid lipofuscinosis, can be transported to lysosomes by the sorting receptor sortillin. But, as summarized here, Zhou et al. describe an alternative route, in which prosaposin links progranulin to another sorting receptor, namely the cation-independent mannose 6-phosphate receptor.

Meanwhile, Paul et al. describe how actin spikes drive 3D cell migration, and Lang et al. explain how defects in ER-mitochondrial contacts can be bypassed by other organelle contact sites. We interview the senior authors of both papers in this month’s biobytes podcast; listen below or subscribe in iTunes!

Biobytes September 14 2015

And don’t forget, of course, to check out the issue’s full table of contents by clicking here!

Cover image showing the kinetochore protein BubR1 (magenta) forming extended filaments on Xenopus mitotic chromosomes (blue) © 2015 Wynne and Funabiki.

New issue: August 31st 2015

In today’s new edition of JCB, Carroll-Portillo et al. reveal that mast cells form physical contacts with dendritic cells to facilitate the transfer of antigens inside exosomes. The dendritic cells can then present these antigens to T cells in order to stimulate an immune response. You can learn more about this new type of immune cell interaction in this week’s In Focus.

Hong et al. demonstrate that the phospholipid PI(3,5)P₂ regulates the dynamics of branched actin networks on the surface of endosomes. As explained here, the phospholipid binds to the actin regulatory protein cortactin, removing it from branched actin filaments so that their stability is decreased. In the absence of PI(3,5)P₂, therefore, cortactin accumulates on late endosomes and actin turnover is reduced.

DeGeer et al. describe how the chaperone protein Hsc70 shepherds a key guanine nucleotide exchange factor to the tips of growing axons. Hsc70 delivers the exchange factor Trio, which activates the small GTPase Rac in response to the axonal guidance cue netrin-1. Embryonic mice expressing a defective form of Hsc70 fail to undergo normal brain development. More here.

Xia et al. describe a way to force cancer cells to destroy a key metabolic enzyme they need to survive. As described here, the researchers find that simultaneously treating cancer cells – but not healthy cells – with inhibitors of both autophagy and the receptor tyrosine kinase FLT3 induces the degradation of hexokinase II, which catalyzes the first step of glycolysis.

Meanwhile, Schweizer et al. describe how a membranous spindle envelope helps numerous proteins accumulate around the mitotic spindle in order to facilitate bipolar spindle assembly and accurate chromosome segregation. Paul Maddox and Anne-Marie Ladouceur comment on the paper here, while senior author Helder Maiato discusses his group’s findings in this month’s biosights video podcast, which you can watch below or subscribe to in iTunes.

And finally, as always, don’t forget to check the JCB table of contents to see all the other papers published in today’s issue!

Cover image showing the accumulation of actin (red) and cortactin (green) on late endosomes (blue) in the absence of PI(3,5)P₂ © 2015 Hong et al.

New issue: August 17th 2015

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

Lawrimore et al. reveal that loops of pericentric chromatin repel each other to generate tension between sister centromeres independently of the mitotic spindle. As explained in this week’s In Focus, the structure of this pericentric chromatin spring may also allow it to act as a shock absorber that can buffer the variable forces generated by dynamic spindle microtubules.

Henne et al. reveal that a protein linked to human neurological disease helps tether vacuoles to the ER in budding yeast. Mutations in human sorting nexin 14 cause an autosomal-recessive form of cerebellar ataxia. Henne et al. find that similar mutations in the yeast homolog, Mdm1, disrupt this protein’s localization to ER-vacuole contact sites, which appears to result in impaired sphingolipid metabolism.

Zhao et al. reveal that the microRNA miR-7 suppresses gastric cancer by inhibiting pro-oncogenic NF-kB signaling. The researchers also find, however, that the NF-kB pathway can inhibit miR-7 expression as part of a feedback signaling loop. Chronic Helicobacter pylori infection is a major risk factor for gastric cancer, and co-culturing the bacterium with gastric epithelial cells activated NF-kB signaling and downregulated miR-7, a potentially key step in gastric cell transformation. More here.

And Hendrix et al. use a series of fluorescence fluctuation imaging techniques to reveal that HIV-1 particles start assembling in the cytoplasm of infected cells. As summarized here, the viral polyprotein Gag starts to oligomerize on viral RNAs in the cytoplasm, before the particles associate with the plasma membrane to complete their assembly into new viral particles.

Meanwhile, in this month’s biobytes podcast, you can hear author Vibe Oestergaard describe how a protein called TopBP1 protects the genome during mitosis (Pedersen et al.), and David Williams explain how defects in phagosome transport lead to age-related macular degeneration (Jiang et al.). Listen below or subscribe in iTunes!

Biobytes August 17 2015

And, of course, there are plenty of other interesting papers, reviews and features for you to discover by visiting our full table of contents page here!

Cover image showing the increased contacts formed between vacuoles and nuclear ER upon Mdm1 overexpression © 2015 Henne et al.

 

New issue: July 20th 2015

In the latest issue of JCB, Strale et al. reveal that interactions between neighboring E-cadherin molecules help to strengthen their connection to the actin cytoskeleton and stabilize cell-cell contacts. As explained here, E-cadherin mutants unable to interact with other E-cadherin molecules in the same membrane can still form intercellular adherens junctions, but these junctions are weaker and cannot coordinate the movements of cells undergoing collective cell migration.

Donovan and Bretscher track the behavior of individual secretory vesicles in budding yeast in order to provide a timeline of the events involved in exocytosis. As detailed in this week’s In Focus, the researchers find that vesicles consistently tether to the bud cortex for 18 seconds before they fuse with the plasma membrane. This tethering period, which may allow cells to ensure vesicles are targeted to the right location, is regulated by the Rab GTPase Sec4p and the myosin motor Myo2p. The researchers also find that Myo2p dissociates from the vesicles about 4 seconds before fusion, in contrast to other components, such as the exocyst complex, that remain bound to vesicles until exocytosis is completed.

Nyathi and Pool describe how a chaperone complex called NAC helps ensure nascent polypeptides are correctly processed as they emerge from ribosomes. Many of the factors that modify, fold, or target nascent polypeptides bind to a particular region of ribosomes called the Universal Adaptor Site. As summarized here, Nyathi and Pool find that NAC regulates the competition between two processing factors: Map1, an enzyme that cleaves the N-terminal methionine off of most cytosolic proteins, and the SRP, which guides nascent secretory and membrane proteins to the ER. Moreover, NAC also prevents nascent secretory proteins from aggregating before they can be recognized by the SRP.

Yan et al. describe how the deubiquitinating enzyme complex BRISC regulates the mitotic spindle assembly factor NuMA. In the absence of BRISC, mitotic cells form disorganized, multipolar spindles because ubiquitinated NuMA shows an increased association with two of its regulators, importin-beta and dynein. More here.

Elsewhere, Bamidele et al. describe how cells regulate the endocytic trafficking and function of the CXCR4 chemokine receptor, and Treuner-Lange et al. explain how a small GTPase combines with bacterial actin to regulate bacterial focal adhesions and motility. You can hear the senior authors of both papers discuss their findings in this month’s biobytes podcast. Listen below or subscribe in iTunes!

Biobytes July 20 2015

 

As always, there are plenty of other interesting papers for you to discover in this week’s issue. You can find them all by visiting our table of contents page here.

Cover image showing the localization of NuMA (green) in monopolar spindles in the presence (bottom) or absence (top) of BRISC subunits © 2015 Yan et al.

 

 

New issue: July 6th 2015

In today’s new edition of JCB, Schouteden et al. reveal that the ciliary transition zone promotes cell adhesion. The transition zone lies between the cilium’s basal body and its microtubule-based axoneme. As explained in this week’s In Focus, Schouteden et al. disrupt this structure in C. elegans, and find that worm neurons are still able to assemble ciliary axonemes, but are unable to extend dendrites, due to a defect in cell-matrix adhesion.

Marshall et al. show that recycling endosomes help cytotoxic T cells kill pathogens and tumor cells by delivering the SNARE protein syntaxin-11 to the immunological synapse where the T cell contacts its target. As summarized here, cytotoxic granules can then fuse and release their contents at this site in order to kill the target cell.

Lim et al. show that hydrogen peroxide at the centrosome spurs cells to advance through mitosis. As described here, hydrogen peroxide levels rise as cells enter mitosis, deactivating the centrosome-localized phosphatase Cdc14B that would otherwise drive immediate mitotic exit. Later in mitosis, cells activate the enzyme peroxiredoxin I at centrosomes in order to lower hydrogen peroxide levels and allow Cdc14B to do its work.

Meanwhile, Lambrus et al. demonstrate that p53 guards the genome by preventing cells with abnormal numbers of centrosomes from dividing. In the absence of p53, cells can continue dividing without centrosomes, resulting in chromosome mis-segregation. More here.

And Lerit et al. describe how a scaffold formed by the proteins centrosomin and PLP maintains the activity of interphase centrosomes in early Drosophila embryos, which is essential for both nuclear spacing and proper chromosome segregation. The authors discuss their work in this month’s biosights podcast, which you can watch below or subscribe to in iTunes.

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

Cover image showing the structure of the ciliary transition zone © 2015 Schouteden et al.

 

New issue: June 22nd 2015

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

Our In Focus paper this week is by Haynes et al., who reveal that a protein called GMFβ helps disassemble the branched actin networks generated by the Arp2/3 complex at the leading edge of migrating fibroblasts, thus promoting lamellipodial retraction and the cells’ ability to navigate towards adhesive directional cues.

Cao et al. reveal that the calcium channel P2X4 stimulates lysosome fusion by releasing calcium ions from the lysosome lumen, thereby recruiting and activating the calcium-binding protein calmodulin.

Amano et al. describe a novel method to identify the substrates of protein kinases. Kinase-Interacting Substrate Screening, or KISS, allowed the researchers to identify both known and unknown targets of several protein kinases. For example, the researchers identified 356 Rho kinase phosphorylation sites on 140 different proteins, including the polarity protein Scrib, which subsequently forms a ternary complex with Rho kinase and the actin-binding protein Shroom2 in order to promote actomyosin contraction at the free edges of epithelial cells. More here.

Seybold et al. describe how three proteins interact to form a structure that initiates the duplication of spindle pole bodies (SPBs), the yeast equivalent of centrosomes. Kar1, Sfi1, and the centrin homolog Cdc31 are all components of the SPB bridge. As summarized here, Seybold et al. find that all 3 proteins stabilize each other’s presence at the bridge and that, while Cdc31 crosslinks rod-shaped Sfi1 molecules to form the bulk of structure, Kar1 keeps the bridge anchored to the nuclear envelope, in which the SPBs are embedded.

Meanwhile, Moyer et al. describe how a protein called STIL promotes mammalian centriole duplication by activating the kinase Plk4. Authors Tyler Moyer and Andrew Holland explain their results in this month’s biobytes podcast, where you can also hear Stella Aronov and Motti Choder discuss their discovery (Aronov et al.) that yeast transport a pheromone-encoding mRNA to the tips of their mating projections in P body-like RNP granules. You can listen below or subscribe in iTunes.

Biobytes June 22 2015

That’s all for today, but there are plenty of other interesting papers for you to discover at our table of contents page here.

 

Cover image of the extended SPB bridge structure formed upon Kar1 overexpression © 2015 Seybold et al.

 

New issue: June 8th 2015

In the latest edition of JCB, Ladouceur et al. investigate what dictates the size of chromosomes in early C. elegans embryos. Chromosomes get increasingly smaller during the early stages of C. elegans development, and, as explained in this week’s In Focus, Ladouceur et al. reveal that this is a response to the decrease in size of both the embryonic cells and their nuclei.

Jiang et al. reveal that migrating neurons generate traction forces at three different regions of the cell. In cerebellar granule cells, these regions – known as contraction centers – localize just behind the tip of the cell’s forward projection, at the base of this projection, and in the cell’s trailing projection. As described here, the relative strength of the forces produced at each of these contraction centers is altered by attractive and repulsive cues that direct the cell’s migration.

Rana et al. demonstrate that alternative splicing transforms a protein that stimulates calcium uptake into one that inhibits it. When calcium levels in the endoplasmic reticulum are low, STIM1 and STIM2 proteins induce Orai channels in the plasma membrane to open up and allow more calcium into the cell. Rana et al. identify a splice variant of STIM2, called STIM2beta, that blocks calcium influx through the Orai1 channel, and which may therefore allow cells to fine tune their calcium dynamics. More here.

And Holtz et al. show that cells secrete an inhibitor of Hedgehog signaling. As summarized here, HHIP1 binds to heparan sulfate molecules in the extracellular matrix, causing the protein to accumulate in basement membranes, where it can control the distribution and activity of Hedgehog ligands.

This month’s biosights video podcast is also out today, highlighting the recent paper by Dennis et al. Senior author Michael Marks describes how the BLOC-2 complex, whose subunits are encoded by genes mutated in Hermansky-Pudlak syndrome, promotes the delivery of melanosomal cargoes by targeting recycling endosomal tubules to maturing melanosomes.

That’s all for today, but, of course, you should visit the JCB’s table of contents page to see all of our latest papers.

Cover image of HHIP1(green) accumulating in the basement membrane underlying the lung epithelium in an E14.5 mouse embryo © 2015 Holtz et al.

 

New issue: May 25th 2015

Yesterday we took some time to remember Alan Hall, and focused on the tributes that appear in the latest edition of JCB. Today, we’ll take a quick look at some of the research highlights published in the same issue.

Wilmes et al. investigate why different type I interferons can trigger different cellular responses, despite binding to the same dimeric cell surface receptor. As discussed in this week’s In Focus, the researchers find that interferon ligands induce dimerization of the receptor subunits IFNAR1 and IFNAR2. The feedback regulator USP18 inhibits receptor dimerization such that only interferons with a relatively high affinity for IFNAR1 can recruit this subunit into the receptor complex and maintain signaling over longer time periods. These interferons can therefore induce different cellular responses than interferons with lower affinity for IFNAR1, which are quickly deactivated by USP18.

Murley et al. identify a yeast protein that might coordinate the function of vacuoles and mitochondria by transferring sterols at the sites where these organelles are contacted by the ER. As described here, the protein, which the researchers name Ltc1, localizes to ER-mitochondria and ER-vacuole contacts, and promotes both mitochondrial function and the stress-induced formation of sterol-rich domains in the vacuole membrane.

Luo et al. describe how the Drosophila ovarian niche limits its own ability to maintain germline stem cells in an undifferentiated state. Wnt signaling within the niche induces expression of the Dpp receptor Tkv, which mops up excess Dpp so that some of the stem cells’ progeny can undergo differentiation. More here.

Smith et al. describe a microscopy technique that instantaneously captures 3D images of live cells, allowing them to track the movement of single mRNAs in the nucleus. As described here, the technique, known as 3D-SMRT, enabled the researchers to image the entire volume of the nucleus 10 times per second, fast enough to track the diffusion of individual β-actin transcripts.

And two papers describe a surprising new role for the mitotic checkpoint proteins BUB1 and BUB3. Kim et al. and Yang et al., working in C. elegans and budding yeast, respectively, show that these proteins, best known for their role in inhibiting anaphase onset if kinetochores aren’t properly attached to the mitotic spindle, also function to promote anaphase onset. You can hear the senior authors of these two studies, Arshad Desai and Soni Lacefield, discuss their findings in this month’s biobytes podcast, where you can also listen to Talila Volk describe her lab’s characterization of a myonuclear scaffold that maintains the shape of muscles in Drosophila larval muscles. You can listen below or subscribe in iTunes.

Biobytes May 25 2015

That’s all for today, but, as always, there are plenty of other interesting articles for you to discover by visiting our table of contents here.

 

Cover image showing the expression of Tkv (red) in a wild-type Drosophila germarium © 2015 Luo et al.

In Memoriam: Alan Hall

There's a new issue of JCB out today. We'll bring you a roundup of the issue's research highlights tomorrow, but, today, we'd like to focus on our tribute to JCB’s Editor-in-Chief Alan Hall. As many of you know, Alan passed away unexpectedly a few weeks ago. To commemorate his life and scientific legacy, this issue contains two memorials.  The first is an account from Alan’s close friend and early collaborator, Chris Marshall, of the start of Alan’s independent scientific career and the events that led to his seminal discoveries and to him becoming the great cell biologist we knew.  The second is a touching tribute from several of Alan’s friends and colleagues.  Their sentiments are echoed by the JCB staff; Alan was on the Editorial Board for 20 years and Editor-in-Chief for too short a period of time.  We can take some small measure of solace in knowing that Alan’s kind and generous spirit will live on through his remarkable scientific legacy.  As we all struggle to express how we feel about his sudden passing and what he meant to us and the community, I created a word cloud (on www.tagul.com) based on key words used to describe Alan in his tribute.  I think this visual summary says it all.  

New issue: May 11th 2015

In today’s new issue of JCB, Stewart et al. reveal that, by organizing both the cytoskeleton and intercellular adhesions, nuclear envelope-spanning LINC complexes help balance forces across cells and tissues. As explained in this week’s In Focus, microtubules are disorganized in epidermal cells lacking the inner nuclear membrane LINC complex component SUN2, disrupting desmosomes and causing Sun2 knockout mice to temporarily lose their hair.

O’Regan et al. reveal that the mitotic kinase Nek6 targets the chaperone Hsp72 to the mitotic spindle, where it promotes the formation of stable K-fibers, the stable microtubule bundles that connect chromosomes to the spindle poles. And, elsewhere in this issue, Prosser et al. demonstrate that the related kinase Nek5 regulates the timing of centrosome separation, another process that orchestrates spindle assembly in mitosis.

Cheng et al. demonstrate that autophagosomes fuse with late endosomes in axonal terminals, a process that allows them to acquire the dynein motors they need to undergo retrograde transport and deliver their contents to lysosomes in the neuronal cell body. More here.

Meanwhile, Pereyra Gerber et al. reveal that the endosomal trafficking protein Rab27a supports HIV-1 replication by promoting production of the phospholipid PI(4,5)P₂ at the plasma membrane of infected cells. As explained here, Rab27a promotes delivery of the late endosome-associated lipid kinase PI4KIIa to the plasma membrane, generating specialized PI(4,5)P2-enriched domains that can recruit the viral assembly protein Gag.

And Grikscheit et al. describe how, in breast epithelial cells cultured in 3D, the formin protein FMNL2 stimulates actin filament assembly at intercellular adhesions downstream of the small GTPase Rac1. Senior author Robert Grosse describes his lab’s results in this month’s biosights video podcast, which you can watch below, or download from iTunes.

That’s all for today, but you can find all of the latest papers published in JCB on our table of contents page here.

 

Cover image of autophagic vacuoles in the neurites of a dorsal root ganglion neuron © 2015 Cheng et al.