Cover image for Vol. 17 Issue 7

Early View (Online Version of Record published before inclusion in an issue)

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. You have full text access to this OnlineOpen article
      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

      Version of Record online: 24 JUN 2016 | 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, internalization 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

      Version of Record online: 23 JUN 2016 | 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. You have full text access to this OnlineOpen article
      Use of BODIPY-Cholesterol (TF-Chol) for Visualizing Lysosomal Cholesterol Accumulation

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

      Version of Record online: 13 JUN 2016 | DOI: 10.1111/tra.12414

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      Dipyrromethene difluoride-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

      Version of Record online: 3 JUN 2016 | 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.

  4. Reviews

    1. HIV-1 Nef: Taking Control of Protein Trafficking

      Estela A. Pereira and Luis L. P. daSilva

      Version of Record online: 3 JUN 2016 | 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.

  5. Original Articles

    1. You have full text access to this OnlineOpen article
      ‘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

      Version of Record online: 2 JUN 2016 | 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 synthesized 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.

  6. Reviews

    1. You have full text access to this OnlineOpen article
      Myosins, Actin and Autophagy

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

      Version of Record online: 31 MAY 2016 | 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.

  7. 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

      Version of Record online: 30 MAY 2016 | 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. You have full text access to this OnlineOpen article
      A Genetic Screen Identifies a Critical Role for the WDR81-WDR91 Complex in the Trafficking and Degradation of Tetherin

      Radu Rapiteanu, Luther J. Davis, James C. Williamson, Richard T. Timms, J. Paul Luzio and Paul J. Lehner

      Version of Record online: 25 MAY 2016 | DOI: 10.1111/tra.12409

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      A genetic screen in human haploid cells identifies a critical role for the WDR81-WDR91 complex in the degradation of tetherin – a potent viral restriction factor. Subsequent experiments show that this complex plays a general role in the degradation of internalized plasma membrane proteins as it is also required for EGFR degradation. Depletion of WDR81 leads to the appearance of markedly enlarged early and late endocytic vesicles and to impaired delivery of cargo to lysosomes.

  8. Reviews

    1. Herpesvirus Entry into Host Cells Mediated by Endosomal Low pH

      Anthony V. Nicola

      Version of Record online: 24 MAY 2016 | DOI: 10.1111/tra.12408

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      Herpesviridae comprise a large family of enveloped DNA viruses that utilize several cellular entry pathways in a cell-type-dependent manner. This review focuses primarily on our understanding of low pH entry mechanisms, with emphasis on the prototype alphaherpesvirus, herpes simplex virus 1 (HSV-1). In our model of infection, HSV-1 enters epithelial cells by a mildly acidic endosomal pathway, and HSV-1 entry into neurons, the site of latency, occurs by direct penetration at the cell surface. Low pH-triggered conformational changes in envelope glycoproteins, particularly the main fusion protein gB, are also described.

  9. Editorial

    1. Editorial Overview: Myosins in Review

      John Kendrick-Jones and Folma Buss

      Version of Record online: 24 MAY 2016 | DOI: 10.1111/tra.12405

  10. Reviews

    1. Cadherin Trafficking for Tissue Morphogenesis: Control and Consequences

      Junior J. West and Tony J. C. Harris

      Version of Record online: 19 MAY 2016 | DOI: 10.1111/tra.12407

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      Tissue morphogenesis often requires the redistribution of cadherin cell–cell adhesion molecules through trafficking. We review the upstream control and downstream consequences of this trafficking in a variety of model systems. We describe how core trafficking machinery integrates with other molecular systems to control cadherin endocytosis, exocytosis and recycling, and how this trafficking has permissive and instructive effects on various aspects of multicellular development.

    2. Tropomyosin-Mediated Regulation of Cytoplasmic Myosins

      Dietmar J. Manstein and Daniel P. Mulvihill

      Version of Record online: 4 MAY 2016 | DOI: 10.1111/tra.12399

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      The metazoan actin-based cytoskeleton facilitates an assortment of diverse cellular functions. This is made possible by the members of the tropomyosin multigene family, which at discrete cellular locations form well-defined copolymers with unique functional properties. Here, we present a unifying theory in which the tropomyosin isoform associating with the actin defines the surface landscape of the copolymer to determine the identity and activity of myosin motors that move upon it.

    3. Mechanics and Activation of Unconventional Myosins

      Christopher Batters and Claudia Veigel

      Version of Record online: 3 MAY 2016 | DOI: 10.1111/tra.12400

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      A model showing an idealized unconventional myosin summarizing some of the mechanical specializations that they possess including the ability to backfold and unfold in the presence of calcium; for calmodulin to bind, rebind and change conformation; to produce the working stroke in two phases; to be dimeric and processive; to sense strain and to alter the kinetics dependent on the external load. The motor domains are shown in blue, the calmodulin/light chains are in yellow.

    4. Structural Basis of Cargo Recognition by Unconventional Myosins in Cellular Trafficking

      Jianchao Li, Qing Lu and Mingjie Zhang

      Version of Record online: 17 MAR 2016 | DOI: 10.1111/tra.12383

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      Unconventional myosins play critical roles in many aspects of cellular tracking processes via binding to different cargo proteins as well as lipid vesicles. This review focuses on the structural basis of cargo recognitions and cargo binding-induced motor activity regulations of several unconventional myosins with prominent roles in cellular trafficking.


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