JCB biowrites

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: 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 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 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.

 

 

New issue: April 13th 2015

In the latest issue of JCB, two papers reveal that the enzyme Sac2 is a phosphoinositide 4-phosphatase that localizes to early endosomes and hydrolyzes PI(4)P. As explained in this week’s In Focus, Nakatsu et al. reveal that Sac2 teams up with the 5 phosphatase OCRL to remove endosomal PI(4,5)P2, while Hsu et al. show that, in the absence of Sac2, PI(4)P accumulates on early endosomes and inhibits endocytic recycling and slows cell migration.

Tsaalbi-Shtylik et al. describe how DNA mismatch repair proteins suppress UV-induced mutagenesis. As summarized here, the mismatch repair proteins Msh2 and Msh6 recognize nucleotides incorrectly incorporated opposite UV-damaged bases by the error-prone process of translesion synthesis, triggering their removal and the activation of DNA damage-signaling and cell cycle arrest.

Roberson et al. demonstrate that the transmembrane protein Tmem231, whose gene is mutated in both Meckel syndrome and orofaciodigital syndrome type 3, regulates ciliary membrane composition by organizing the organelle’s transition zone. More here.

Scheffler et al. reveal how two minus end-directed microtubule motors work in parallel to bring haploid nuclei together during fission yeast mating. As explained here, the kinesin motor Klp2 localizes to microtubules emanating from the spindle pole bodies associated with each haploid nucleus, and could potentially bring the nuclei together by sliding antiparallel microtubules past each other. Dynein, in contrast, localizes to the spindle pole bodies themselves, where it might pull on microtubules emanating from the other nucleus once Klp2 has brought them into close proximity.

And Juanes-Garcia et al. describe how a short, serine-rich motif in the non-helical tail domain of myosin II-B enables this motor protein to form stable actomyosin bundles that define the rear of migrating mesenchymal cells. Fenix and Burnette provide a commentary on the finding’s significance here, and senior author Miguel Vicente-Manzanares discusses his lab’s work in this month’s biosights video podcast. You can watch below or subscribe in iTunes.

That’s all for today, but you can find lot’s of other interesting papers to read on our table of contents here.

Cover image showing Tmem231 (green) at the ciliary transition zone between the basal body (red) and axoneme (blue) © 2015 Roberson et al.  

New issue: March 16th 2015

In the latest issue of JCB, two papers describe how different nuclear pore complex proteins affect cell differentiation and aging. Gomez-Cavazos and Hetzer reveal that the nucleoporin Nup210 promotes muscle differentiation by maintaining nuclear envelope and ER homeostasis, thereby suppressing an ER stress-specific cell death pathway. And Lord et al. demonstrate that nucleoporins directly affect yeast cell aging. Removing a critical domain from Nup116, for example, decreases yeast replicative lifespan, apparently by inhibiting the nucleocytoplasmic transport of factors required to maintain mitochondrial function. You can read a summary of both papers in this week’s In Focus.

Meanwhile, Sohet et al. demonstrate that the tricellular tight junction protein LSR helps form the blood-brain barrier during embryogenesis. Moreover, the researchers find that LSR is downregulated in mouse models of both multiple sclerosis and stroke, suggesting that the loss of this protein could explain why the blood-brain barrier is disrupted in these, and other, neurological disorders. More here.

Donninger et al. reveal that the Ras effector NORE1A induces cell senescence and suppresses tumorigenesis by promoting the acetylation of p53. As explained here, Ras promotes NORE1A’s association with a kinase called HIPK2, which, in turn, enhances p53 acetylation and cell senescence, protecting cells from oncogenic Ras mutations.

Tian et al. reveal how Hedgehog signaling prompts Drosophila intestinal stem cells to proliferate in response to injury. As described here, Hedgehog doesn’t act on the stem cells themselves but rather on neighboring enteroblasts that consequently upregulate the cytokine Upd2, which stimulates stem cell proliferation by activating the JAK/STAT signaling pathway. Tian et al. also demonstrate that JNK signaling acts upstream to induce Hedgehog ligand production in response to intestinal injury.

And Luu et al. describe how the protocadherin PAPC promotes tissue separation in early Xenopus and zebrafish embryos, in part by downregulating planar cell polarity proteins at the ectoderm-mesoderm boundary. The researchers also identify a novel type of cell-cell contact – which they term a ‘cleft contact’ – in which cells are attached to each other but remain separated by a narrow gap. You can read a commentary about the study by David Wilkinson here, and co-senior author Rudolf Winklbauer explains the group’s findings in the latest biosights video, which you can watch below or in iTunes.

There are lots of other interesting papers for you to discover on our table of contents page, where you'll also find the latest feature in our 60th anniversary series, in which Bas van Steensel provides a fascinating guide to developing new technologies in the lab. It could be very useful for a lot of you out there, I'm sure!

Cover image showing LSR (red) at the tricellular tight junctions of brain blood vessels (green) © 2015 Sohet et al.

 

New issue: February 16th 2015

In the latest issue of JCB, Mourier et al. reveal that the mitochondrial fusion protein Mitofusin 2 is required to maintain production of the respiratory chain cofactor coenzyme Q. As explained here, deleting Mitofusin 2 downregulates several components of the terpenoid biosynthetic pathway that synthesizes key precursors of coenzyme Q. Supplementing Mitofusin 2-deficient cells with the coenzyme partially restores mitochondrial function, suggesting that this approach could ameliorate the symptoms of patients with diseases, such as Charcot-Marie-Tooth type 2A, that are caused by mutations in the Mitofusin 2 gene.

Klebba and Galletta et al. reveal that the scaffold protein Asterless regulates centriole duplication by controlling turnover of the kinase Plk4. Asterless’ role in centriole duplication was thought to be limited to recruiting Plk4 to centrioles during mitosis. But Klebba and Galletta et al. now show that, in part through a newly identified Plk4-binding site, Asterless stabilizes the kinase during mitosis while promoting its turnover during interphase. More here.

Fennell et al. demonstrate that centromeres can stand in for telomeres to promote assembly of the fission yeast meiotic spindle. During meiotic prophase, the clustering of telomeres near the spindle pole body (the yeast equivalent of the centrosome) helps this structure insert into the nuclear envelope and assemble a bipolar spindle. As summarized in this article, Fennell et al. show that, in the absence of telomere clustering, centromeric chromatin can perform the same function as telomeres by contacting spindle pole bodies and promoting the recruitment of the inner nuclear membrane SUN protein Sad1.

Two papers by Comrie et al. (here and here) describe how actin functions on both sides of the immunological synapses that form between T cells and antigen-presenting cells. As summarized in this week’s In Focus, the researchers find that actin helps immobilize ICAM-1 on the surface of antigen-presenting dendritic cells. By binding to the T cell integrin LFA-1, immobilized ICAM-1 resists the forces exerted by the T cell’s actin cytoskeleton, generating tension that promotes LFA-1’s conversion to an active, high-affinity conformation that enhances T cell activation.

And Johnson et al. reveal that filopodial protrusions initiate and orient lamellipodia at the leading edge of migrating fibroblasts, helping the cells to navigate gradients of immobilized guidance cues. Senior author Jason Haugh describes his lab's results in more detail in this month’s biosights video podcast, available below or on iTunes.

And finally for today, I’d like to point you in the direction of our latest article celebrating JCB’s 60^th anniversary. I’ll let our reviews editor, Priya Prakash Budde, explain more:

JCB has a rich history of publishing groundbreaking cell biology, some of which we are highlighting to commemorate our 60th anniversary.  But we are not content to rest on our laurels; as part of our celebrations, we have asked cell biologists and scientists straddling other disciplines to provide their perspective on what is cell biology today and where it is going. These articles will cover some prominent topics such as the integration of the physical sciences with cell biology, as well as take a moment to reflect on some aspects that have been lost.  For example, today’s article from Graham Warren reminds us that many of cell biology’s breakthroughs were discovered in unusual model organisms, and our quest for molecular mechanism has come at the expense of exploring the remarkable cellular diversity in nature.  As other experts comment on a variety of topics from technology development to synthetic cell biology, we hope that their diverse opinions will further convince you of the relevance of cell biology and how it extends far beyond the cell.  Stay tuned this year as we take turns to look back and look forward. We hope you enjoy the ride!

 

Cover image of mitochondria (magenta) in a cardiomyocyte lacking Mitofusin 2 © 2015 Mourier et al.

 

New issue: January 19th 2015

In today’s new edition of JCB, Ducuing et al. identify a feed-forward signaling loop that allows Drosophila embryos to complete the process of dorsal closure. As explained in this week’s In Focus, the loop, which involves the signaling proteins JNK and DPP, helps embryos complete morphogenesis in the face of environmental and genetic challenges.

Otomo et al. demonstrate that B cells need the protein-sorting signal mannose 6-phosphate to proliferate, differentiate, and present antigens. As described here, in the absence of mannose 6-phosphate synthesis – a feature of the human disease mucolipidosis II – B cells can’t target proteases to lysosomes to process and present antigens, which therefore inhibits the cells’ ability to mature and produce antibodies.

LeClaire et al. identify a kinase that helps activate the actin-nucleating Arp2/3 complex. Nck-interacting kinase, or NIK, phosphorylates Arp2 and induces actin polymerization and membrane protrusion in response to epidermal growth factor. More here.

Shibuya et al. identify a protein complex that helps return wandering proteins back to the ER. As summarized here, the authors identify a protein complex consisting of the Golgi proteins Erv41 and Erv46, which binds to escaped ER proteins and returns them home in COPI vesicles.

And Craft et al. reveal that the intraflagellar transport of tubulin is specifically upregulated in regenerating cilia so that large amounts of the protein can be delivered to the growing ends of the organelles’ microtubules. Senior author Karl Lechtreck describes his group’s findings in this month’s biosights video, which you can watch below or subscribe to in iTunes. And if you’d like to discuss the implications of this study with your colleagues, don’t forget you can download everything you could possibly need for a Journal Club presentation here.

Cover image showing lysosomal storage material accumulating in mannose 6-phosphate-deficient B cells © 2015 Otomo et al.

 

New issue: December 22nd 2014

In today’s new edition of JCB, Nunes Bastos et al. describe how the kinesin motor KIF4A restricts its own activity during mitosis. The mitotic kinase Aurora B phosphorylates KIF4A to promote the kinesin’s localization to the anaphase central spindle and activate its ability to suppress microtubule growth. But, as summarized here, Nunes Bastos et al. find that KIF4A in turn recruits two isoforms of the phosphatase PP2A-B56, which dephosphorylate and inactivate the kinesin, allowing the central spindle to fully extend and push sister chromatids apart during anaphase.

Galati et al. identify a protein that helps cilia basal bodies respond to mechanical force so that they maintain their organization in multi-ciliated Tetrahymena cells. DisAp localizes to basal body auxillary structures called kinetodesmal, or striated, fibers, and it helps these structures extend toward the cell cortex when cilia experience more mechanical force, maintaining the basal bodies’ alignment and orientation so that their attached cilia all beat in the same direction. More here.

Lorenzo et al. reveal that the adaptor protein ankyrin-B promotes the axonal transport of multiple organelles by linking the dynein motor accessory factor dynactin to membrane phospholipids. As explained here, ankyrin-B binds to PI(3)P on the surface of endosomes, lysosomes, synaptic vesicles, and mitochondria, and recruits dynactin to these organelles to promote their transport along microtubules, a process essential for axonal growth.

And Gault et al. describe how differences in osmotic pressure between epithelial tissues and their external environment help initiate the tissue’s wound response. Senior author Philipp Niethammer explains in both this week’s In Focus and this month’s biosights video podcast, the osmolarity of the external environment stimulates wound closure in zebrafish by inducing ATP release and epithelial cell migration.

That’s all for today - and all for this year! - but don’t forget to visit our table of contents to catch up on all the latest papers. Happy Holidays!

Cover image of basal bodies (red) and kinetodesmal fibers (green) in a multi-ciliated Tetrahymena cell © 2014 Galati et al.

New issue: November 24th 2014

In today’s new edition of JCB, Baßler et al. describe how a motor protein on immature ribosomes connects to a network of other molecules within the nascent organelles so that it can tug them into their final positions. As described in this week’s In Focus, the dynein-related motor Rea1 removes a protein called Rsa4 from immature ribosomes and, in the process, appears to reposition several other ribosomal components into their correct locations.

Fernandes et al. reveal that mutations in the Drosophila gene Skywalker, a homologue of a human gene linked to neurodegeneration and epilepsy, enhances the turnover of old synaptic vesicle-associated proteins. This increases the abundance of newer, more active synaptic vesicle proteins, which, by enhancing synaptic activity, could result in neurodegeneration. More here.

Juin et al. identify a receptor that allows cancer cells to recognize and break through type I collagen. As explained here, the collagen receptor DDR1 promotes the formation of actin-rich extensions called linear invadosomes by activating the small GTPase Cdc42 through its guanine nucleotide exchange factor Tuba. The linear invadosomes then degrade the extracellular collagen matrix to promote cance cell invasion.

And Sun et al. reveal that oscillating calcium levels help melanoma cells become invasive. Calcium waves induced by the proteins STIM1 and Orai1 stimulate invadosome protrusions and promote the delivery of a matrix metalloproteinase to the plasma membrane. More here.

And finally for today, Jones et al. reveal that dynein’s light intermediate chains are required to maintain centrosome integrity during mitosis, preventing the premature separation of mother-daughter centrioles and the formation of multipolar spindles. Senior authors Viki Allan and Sarah Woolner explain more in this month’s biosights video podcast, which you can watch below or subscribe to in iTunes.

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

Cover image of linear invadosomes in a breast cancer cell © 2014 Juin et al.