Cover image for Vol. 17 Issue 10

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. Case Reports

    1. Characterization of a caveolin-1 mutation associated with both PAH and congenital generalized lipodystrophy

      Bing Han, Courtney A. Copeland, Yumeko Kawano, Erika Berman Rosenzweig, Eric D. Austin, Layla Shahmirzadi, Sha Tang, Krishnan Raghunathan, Wendy K. Chung and Anne K. Kenworthy

      Accepted manuscript online: 26 SEP 2016 09:10AM EST | DOI: 10.1111/tra.12452

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      We identify a heterozygous F160X mutation in the caveolin-1 (CAV1) gene in a patient with both pulmonary arterial hypertension (PAH) and congenital generalized lipodystrophy (CGL) and examine its effect on caveolae assembly. We find that the mutant protein forms hybrid caveolae together with wild type CAV1 in patient skin fibroblasts and reconstituted CAV1−/− MEFs but that these caveolae are abnormal in several respects. These caveolaer defects may serve as contributing factors to the development of PAH and CGL.

  2. Original Articles

    1. Vps35-dependent recycling of Trem2 regulates microglial function

      Jie Yin, Xiaocui Liu, Qing He, Lujun Zhou, Zengqiang Yuan and Siqi Zhao

      Accepted manuscript online: 26 SEP 2016 09:10AM EST | DOI: 10.1111/tra.12451

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      Model for Vps35-mediated Trem2 recycling. Wild type Trem2 is internalized in a clathrin-dependent manner then trafficked to cell membrane through Vps35. By recycling Trem2, Vps35 is involved in suppressing pro-inflammatory responses of microglia. However, the R47H mutant Trem2 is impaired in interacting with Vps35 and accumulated in lysosome for degradation.

    2. Newly synthesized and recycling pools of the apical protein gp135 do not occupy the same compartments

      Emily H. Stoops, Michael Hull and Michael J. Caplan

      Accepted manuscript online: 20 SEP 2016 10:00AM EST | DOI: 10.1111/tra.12449

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      In polarized epithelial cells, apical or basolateral membrane proteins are sorted in endosomal compartments en route to their target membranes. We used the SNAP tag system to study the intracellular trafficking of the apical protein gp135. Newly synthesized gp135 was shown to traverse the apical recycling endosome (ARE), while post-endocytic gp135 was delivered to the early endosome (AEE) before recycling to the apical membrane. The lack of overlap in the pathways of the newly synthesized and recycling pools of gp135 may represent a mechanism for differential sorting.

  3. Reviews

    1. Cadherin Tales: Regulation of Cadherin Function by Endocytic Membrane Trafficking

      Chantel M. Cadwell, Wenji Su and Andrew P. Kowalczyk

      Accepted manuscript online: 14 SEP 2016 12:20AM EST | DOI: 10.1111/tra.12448

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      Cellular rearrangements during development, wound healing, and metastasis require dynamic regulation of adhesion. Endocytic membrane trafficking has emerged as a fundamental mechanism by which cells confer plasticity to adhesive junctions. Recent studies indicate that the juxtamembrane domain of classical cadherins contains multiple endocytic motifs, or “switches”, that can be used by cellular membrane trafficking machinery to regulate adhesion. This review focuses on p120-catenin and other cadherin binding proteins, ubiquitin ligases, and growth factors as key modulators of cadherin membrane trafficking.

  4. Toolbox

    1. Cresyl violet: a superior fluorescent lysosomal marker

      Philip P. Ostrowski, Gregory D. Fairn, Sergio Grinstein and Danielle E. Johnson

      Accepted manuscript online: 13 SEP 2016 04:20AM EST | DOI: 10.1111/tra.12447

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      We have identified cresyl violet as a superior fluorescent lysosomal marker. This red-shifted fluorophore accumulates selectively in lysosomes in a pH-dependent manner. Furthermore, we find that cresyl violet is remarkably photostable and does not photoconvert to other fluorescent species, unlike other widely used lysosomal probes. Cresyl violet does not alter the lysosomal buffering capacity, membrane integrity or luminal pH, it is widely available, and costs ≈ 30,000 times less than competing probes.

  5. Traffic Interchanges

    1. An antimicrobial origin of transit peptides accounts for early endosymbiotic events

      Francis-André Wollman

      Accepted manuscript online: 13 SEP 2016 03:35AM EST | DOI: 10.1111/tra.12446

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      Primary endosymbiosis, which gave rise to mitochondria or chloroplasts, required successful targeting of a number of proteins from the host cytosol to the endosymbiotic organelles. A survey of studies published in separate fields of biological research over the past forty years argue for an antimicrobial origin of targeting peptides. It is proposed that mitochondria and chloroplast derive from microbes that developed a resistance strategy to antimicrobial peptides that consisted in their rapid internalization and proteolytic disposal by microbial peptidases.

  6. Toolbox

    1. You have full text access to this OnlineOpen article
      Using HHsearch to tackle proteins of unknown function – a pilot study with PH domains

      David R. Fidler, Sarah E. Murphy, Katherine Courtis, Pantelis Antonoudiou, Rana El-Tohamy, Jonathan Ient and Timothy P. Levine

      Accepted manuscript online: 7 SEP 2016 03:05AM EST | DOI: 10.1111/tra.12432

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      HHsearch (available online as HHpred) is a powerful bioinformatics tool that examines the predicted 3D structure of a protein to detect remote protein homologies. We have applied HHsearch to study a single structural fold (PH and PH-like domains) in a single model organism (yeast) as proof of principle. HHsearch detected known domains in yeast with 99% specificity as well 16 new PH-like domains in 13 proteins. We corroborated the functional importance of one predicted domain in Vps13. Similar remote homology searches should be applied genome-wide.

  7. Original Articles

    1. Distinct roles of the two VPS33 proteins in the endolysosomal system in Caenorhabditis elegans

      Keiko Gengyo-Ando, Eriko Kage-Nakadai, Sawako Yoshina, Muneyoshi Ohtori, Yuko Kagawa-Nagamura, Junichi Nakai and Shohei Mitani

      Accepted manuscript online: 25 AUG 2016 03:46AM EST | DOI: 10.1111/tra.12430

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      Metazoan cells have two Vps33 proteins, VPS33A and VPS33B, which are thought to participate in endocytic membrane trafficking, but their precise roles remain unknown. Here, we used null mutant Caenorhabditis elegans to demonstrate that VPS-33.1 (VPS33A) is essential for viability and both early and late fusion events in the endocytic pathway, whereas VPS-33.2 (VPS33B) is not essential for these events but is required for spermatogenesis. Thus, animals might use these two proteins in distinct contexts.

    2. Rab24 interacts with the Rab7/RILP complex to regulate endosomal degradation

      Celina Amaya, Rodrigo D. Militello, Sebastián D. Calligaris and María I. Colombo

      Accepted manuscript online: 23 AUG 2016 02:55AM EST | DOI: 10.1111/tra.12431

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      The Rab GTPases family coordinates the endocytic pathway. We have found Rab24 as a component of the endosome-lysosome degradative route. We demonstrate that Rab24 forms a complex with Rab7 and RILP on the membranes of LE, and its activity is essential for Rab7 membrane recruitment and DQ-BSA degradation. Additionally, overexpression of the HOPS subunit Vps41 hampered the Rab24/RILP association. Our data support that Rab24 owns a molecular function in the last steps of the endosomal degradative pathway via its interaction with critical components of the pathway.

    3. You have free access to this content
      Tracking adenovirus genomes identifies morphologically distinct late DNA replication compartments

      Tetsuro Komatsu, Derrick R. Robinson, Miharu Hisaoka, Shuhei Ueshima, Mitsuru Okuwaki, Kyosuke Nagata and Harald Wodrich

      Accepted manuscript online: 5 AUG 2016 02:41AM EST | DOI: 10.1111/tra.12429

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      The spatial relationship between early adenoviral genome replication and subsequent viral gene expression has been established. In contrast when and where newly replicated genomes are linked to progeny virion production remains unclear. Using direct genome-labeling techniques, we show the formation of a novel subnuclear compartment late in infection, which we named ViPR body that functions as a reservoir for replicated adenoviral genomes, and identified a host factor specifically localizing in the domain. The potential role of ViPR bodies is discussed.

    4. You have full text access to this OnlineOpen article
      KIF1A mediates axonal transport of BACE1 and identification of independently moving cargoes in living SCG neurons

      Christy O.Y. Hung and Michael P. Coleman

      Accepted manuscript online: 3 AUG 2016 03:20AM EST | DOI: 10.1111/tra.12428

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      Using two-colour live-cell imaging, we found that KIF1A is the primary anterograde motor protein mediating the axonal transport of BACE1. We further identified several cargoes that have little or no co-migration with KIF1A-GFP and also move independently from BACE1-mCherry. Our findings suggest that axonally transported cargoes are sorted into different classes of carrier vesicles in the cell body and are transported by cargo-specific motor proteins through the axon.


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