Cover image for Vol. 17 Issue 6

Accepted Articles (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Edited By: Michael S. Marks, Trina A. Schroer, Tom H. Stevens and Sharon A. Tooze

Online ISSN: 1600-0854


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  1. Original Articles

    1. Alphavirus restriction by IFITM proteins

      Stuart Weston, Stephanie Czieso, Ian J. White, Sarah E. Smith, Rachael S. Wash, Carmen Diaz-Soria, Paul Kellam and Mark Marsh

      Accepted manuscript online: 24 MAY 2016 02:35AM EST | DOI: 10.1111/tra.12416

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      IFITM3 can inhibit cellular infection by two alphaviruses, Sindbis and Semliki Forest virus (SFV). IFITM2 has lower antiviral activity, and IFITM1 does not restrict either virus through the endocytic route of infection. IFITM3 does not inhibit SFV binding, internalisation into cells, trafficking to endosomes or low pH-induced conformational changes in the E1 fusion protein. However, the viral capsid is not released into the cytosol in IFITM3 expressing cells.

    2. Distinct roles for APPL1 and APPL2 in regulating Toll-like receptor 4 signaling in macrophages

      Jeremy C. Yeo, Adam A. Wall, Lin Luo, Nicholas D. Condon and Jennifer L. Stow

      Accepted manuscript online: 24 MAY 2016 02:31AM EST | DOI: 10.1111/tra.12415

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      APPLs 1 and 2 are common signaling adaptors but their roles in macrophages are largely uncharacterized. We show that both APPL1 and APPL2 are associated with surface ruffles and macropinocytic membranes in activated macrophages where they contribute to signaling and transcription downstream of the pathogen-stimulated Toll-like receptor, TLR4. The APPLs exert disparate, sometimes opposing regulation that helps to shape the inflammatory cytokine program for innate immune responses.

  2. Traffic Interchanges

    1. Use of BODIPY-cholesterol (TF-Chol) for visualizing lysosomal cholesterol accumulation

      Maarit Hölttä-Vuori, Erdinc Sezgin, Christian Eggeling and Elina Ikonen

      Accepted manuscript online: 17 MAY 2016 07:35AM EST | DOI: 10.1111/tra.12414

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      BODIPY-cholesterol (TopFluor-Cholesterol) is a widely used cholesterol analogue due to its excellent fluorescence properties and considerable similarity with natural cholesterol in terms of membrane partitioning. However, specific concerns were recently raised about its suitability to detect lysosomal cholesterol accumulation. Here, we provide an explanation to these apparent discrepancies and offer practical suggestions for using this probe in visualizing lysosomal cholesterol accumulation.

  3. Original Articles

    1. Identification and characterization of LIN-2(CASK) as a regulator of kinesin-3 UNC-104(KIF1A) motility and clustering in neurons

      Gong-Her Wu, Muniesh Muthaiyan Shanmugam, Prerana Bhan, Yu-Hsin Huang and Oliver Ingvar Wagner

      Accepted manuscript online: 12 MAY 2016 08:31AM EST | DOI: 10.1111/tra.12413

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      LIN-2 and SYD-2 are both active zone proteins that interact with UNC-104 on overlapping binding regions. LIN-2 interacts with the motor via its L27 and GUK domains which also interact with the coiled coils and SAM domains of SYD-2. While the absence of SYD-2 leads to a reduction in axonal motor clustering, the absence of LIN-2 increases clustering. Both LIN-2 and SYD-2 positively regulate the velocity of UNC-104, however, only LIN-2 is able to efficiently elevate the motor's run lengths.

    2. ‘2A-Like’ Signal Sequences Mediating Translational Recoding: A Novel Form of Dual Protein Targeting

      Claire Roulston, Garry A. Luke, Pablo de Felipe, Lin Ruan, Jonathan Cope, John Nicholson, Andriy Sukhodub, Jens Tilsner and Martin D. Ryan

      Accepted manuscript online: 10 MAY 2016 04:36AM EST | DOI: 10.1111/tra.12411

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      We describe ‘2A-like’ oligopeptide sequences, found as N-terminal features, which are able to mediate translational recoding - but also to function as a signal sequence. If 2A mediates translational recoding, the 2A signal sequence is synthesised as a discrete translation product separate from the downstream product. If 2A does not mediate translational recoding, the 2A signal sequence is fused to the downstream translation product, functions as a signal sequence and targets the fusion protein to the exocytic pathway.

  4. Reviews

    1. HIV-1 Nef: taking control of protein trafficking

      Estela A. Pereira and Luis L. P. daSilva

      Accepted manuscript online: 10 MAY 2016 04:35AM EST | DOI: 10.1111/tra.12412

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      The Nef protein of the Human Immunodeficiency Virus modifies the surface proteome of infected cells in order to create an optimized environment for viral replication and to enhance the infectivity of newly produced virions. Nef achieves this goal by hijacking membrane trafficking pathways to keep specific immune receptors, signaling molecules and viral restriction factors away from the plasma membrane. This review focuses on how Nef interferes with protein trafficking by physically linking target surface proteins to components of protein sorting machinery.

    2. You have full text access to this OnlineOpen article
      Myosins, actin and autophagy

      Antonina J. Kruppa, John Kendrick-Jones and Folma Buss

      Accepted manuscript online: 5 MAY 2016 02:05AM EST | DOI: 10.1111/tra.12410

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      Autophagy is an essential degradation pathway that delivers cytosolic components to the lysosome. This pathway recycles macromolecules for energy production and clears the cytosol from damaged proteins, organelles and invading pathogens. In this review, we will discuss the importance of actin filament dynamics for autophagy progression and highlight the distinct requirement for three classes of myosins during different stages of the autophagy pathway.

  5. Original Articles

    1. You have full text access to this OnlineOpen article
      Molecular Mechanisms of Disease Pathogenesis Differ in Krabbe Disease Variants

      Samantha J. Spratley, Chris H. Hill, Agnete H. Viuff, James R. Edgar, Karsten Skjødt and Janet E. Deane

      Accepted manuscript online: 29 APR 2016 03:01AM EST | DOI: 10.1111/tra.12404

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      Krabbe disease is a devastating neurodegenerative disorder caused by defects in the lysosomal hydrolase galactocerebrosidase (GALC). Over 100 different mutations have been identified in the GALC gene and are located throughout the protein. Here, we identify a number of distinct molecular mechanisms underlying the disease pathogenesis, including misfolding and incorrect post-translational modification resulting in the lack of delivery of GALC (green) to lysosomal compartments (red, cathepsin D). Understanding these molecular defects will aid the targeting of specific new therapeutics for this fatal disease.

    2. N-cadherin regulates cell migration through a Rab5-dependent temporal control of macropinocytosis

      Meng-Hsuan Wen, Jen-Yeu Wang, Yu-Ting Chiu, Mei-Pin Wang, Sue-Ping Lee and Chin-Yin Tai

      Accepted manuscript online: 8 APR 2016 01:06PM EST | DOI: 10.1111/tra.12402

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      Macropinocytosis is a clathrin-independent endocytic pathway implicated in cell migration. We show that lateral clustering of N-cadherin forms specialized micro-domains involved in the recruitment of Rab5 at the macropinosomes. De-clustering of N-cadherin drives Rab5-to-Rab7 conversion and promotes macropinosome maturation. Consequently, both centripetal trafficking of macropinosomes and wound-induced migration are accelerated. These results suggest a new role for N-cadherin in cell migration through temporal control of macropinocytosis.


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