In today’s new issue of JCB, Zhang et al. reveal that inhibitors of a metabolic enzyme restore mRNA nuclear export to cells infected with the influenza virus. The flu virus shuts off gene expression in its host cell by producing a protein called NS1 that inhibits the processing and nuclear export of host cell mRNAs. Zhang et al. find that inhibitors of dihydroorotate dehydrogenase, an enzyme required for the de novo synthesis of pyrimidines like cytosine and thymine, restore mRNA export to infected cells and inhibit viral replication, in part by boosting levels of an mRNA export factor. More here.
Oakes et al. suggest that actin filament stress fibers may serve as templates to promote the growth and maturation of focal adhesions. As described in this week’s In Focus, focal adhesions fail to mature in cells unable to form stress fibers near nascent cell attachments. Myosin II-generated tension has been thought to play a vital role in driving maturation, but Oakes et al. show that tension is still transmitted to focal adhesions in the absence of radial stress fibers, and tension can be reduced by as much as 80% without inhibiting adhesion maturation. “You need a sufficient amount of tension… but maturation isn't a tension-dependent process above that threshold,” says senior author Margaret Gardel, who thinks that the radial stress fibers may serve as structural templates to recruit additional focal adhesion proteins.
Staying with focal adhesions, Wang and McNiven describe how they recruit a matrix metalloproteinase to degrade the extracellular matrix and promote tumor cell invasion. The protease MT1 is brought to cell-matrix attachments by the focal adhesion proteins p130Cas and FAK, and it digests the surrounding ECM independently of another matrix-degrading structure in tumor cells, the invadopodium. You can read more in this summary, in which senior author Mark McNiven suggests that focal adhesions could cluster at the leading edge of invading cells to clear a path through the ECM.
Elsewhere, Ivanovic et al.describe how a glial cytoskeletal adaptor protein called 4.1G helps to spatially organize membrane proteins in both myelinating Schwann cells and the neuronal axons they ensheath. (Summary here). Nechipurenko and Broihier reveal that the transcription factor FoxO limits the stability of neuronal microtubules, and that this activity is restricted when neurons suffer cytoskeltal damage. And Christis and Munro show that the Arl1 GTPase controls the local activation of another small G protein, Arf1, to promote the formation of transport vesicles at the trans face of the Golgi apparatus. You can learn more about these latter two papers from the authors themselves, who feature in this month’s biobytes podcast. Listen below or subscribe in iTunes.
Cover image courtesy of Yvonne Beckham and Patrick Oakes.
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