Cover image for Vol. 16 Issue 12

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, Sharon A. Tooze

Online ISSN: 1600-0854


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  1. Original Articles

    1. Human peroxin PEX3 is co-translationally integrated into the ER and exits the ER in budding vesicles

      Peter U. Mayerhofer, Manuel Bañó-Polo, Ismael Mingarro and Arthur E. Johnson

      Accepted manuscript online: 17 NOV 2015 04:10AM EST | DOI: 10.1111/tra.12350

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      Some peroxisomal membrane proteins (PMPs) are targeted first to the ER prior to being transported to peroxisomes. The mechanisms that mediate ER-passage of PMPs in mammalians are unknown. We demonstrate that the human PMP PEX3 inserts co-translationally into the ER by an SRP/Sec61-translocon dependent multistep pathway. Subsequently, PEX3 exits the ER via budding vesicles in an energy-consuming reaction. Hence, we demonstrate how the ER is seeded with PMPs, and highlight the significance of ER-to-peroxisome vesicle trafficking in human organelle biogenesis.

    2. The Sec1/Munc18 Protein Groove plays a Conserved Role in Interaction with Sec9p/SNAP-25

      Marion Weber-Boyvat, Konstantin G. Chernov, Nina Aro, Gerd Wohlfahrt, Vesa M. Olkkonen and Jussi Jäntti

      Accepted manuscript online: 17 NOV 2015 02:30AM EST | DOI: 10.1111/tra.12349

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      The events orchestrating vesicle targeting and fusion at the plasma membrane are poorly understood. The Sec1/Munc18 proteins have an essential role in SNARE-mediated membrane fusion. We show in yeast and mammalian cells that “the groove”, a recently identified protein interaction site in Sec1p, plays an important role in mediating interactions with Sec9p/SNAP-25. “The groove” represents an evolutionarily conserved site for Sec9p/SNAP-25 binding and plays, in concert with Sro7p, a regulatory role in initial steps of exocytic SNARE complex assembly.

  2. Toolbox

    1. Readily Accessible Multiplane Microscopy: 3D Tracking the HIV-1 Genome in Living Cells

      Michelle S. Itano, Marina Bleck, Daniel S. Johnson and Sanford M. Simon

      Accepted manuscript online: 14 NOV 2015 04:17AM EST | DOI: 10.1111/tra.12347

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      The trafficking of HIV-1 genomic RNAs from sites of replication in the nucleus, through the cytoplasm, to sites of assembly at the plasma membrane is critical for HIV-1 viral replication. We present a broadly accessible microscopy method that captures multiple focal planes simultaneously, enabling high-resolution 3D imaging of a single macromolecule. We show that HIV-1 genomic RNAs are most mobile in the cytosol, and undergo confined mobility at sites along the nuclear envelope and in the nucleus and nucleolus.

  3. Original Articles

    1. Phosphorylation of αSNAP is required for secretory organelle biogenesis in Toxoplasma gondii

      Rebecca J. Stewart, David J. P. Ferguson, Lachlan Whitehead, Clare H. Bradin, Hong J. Wu and Christopher J. Tonkin

      Accepted manuscript online: 14 NOV 2015 12:53AM EST | DOI: 10.1111/tra.12348

      Synopsis Stewart et al show that phosphorylation of alpha-SNAP a protein required for turnover of SNARE complexes after vesicle fusion is important for secretory pathway protein trafficking and organelle biogenesis in Toxoplasma gondii. This work therefore highlights a potential mechanism of regulation of secretory pathway biogenesis during growth in this important pathogen

    2. Phosphatidylinositol 3,5-bisphosphate-rich membrane domains in endosomes and lysosomes

      Sho Takatori, Tsuyako Tatematsu, Jinglei Cheng, Jun Matsumoto, Takuya Akano and Toyoshi Fujimoto

      Accepted manuscript online: 13 NOV 2015 02:38AM EST | DOI: 10.1111/tra.12346

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      PtdIns(3,5)P2 is a minor phospholipid but it has critical functions in endosomes/lysosomes, and its deficiency is linked to neurodegenerative diseases including amyotrophic lateral sclerosis. Using a new electron microscopic method to define the nanolevel distribution, PtdIns(3,5)P2 was found to have a biased distribution in yeast vacuoles exposed to high salt stress and in mammalian endosomes with tubulo-vesicular morphology. Segregation of PtdIns(3,5)P2-rich and -deficient domains should be important in understanding endosome/lysosome functionality.

  4. Reviews

    1. The crossroads of synaptic growth signaling, membrane traffic, and neurological disease: Insights from Drosophila

      Mugdha Deshpande and Avital A. Rodal

      Accepted manuscript online: 5 NOV 2015 03:52AM EST | DOI: 10.1111/tra.12345

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      Neuronal growth factor signaling is highly dependent on membrane traffic, both for the packaging and release of the growth factors themselves, and for regulation of intracellular signaling by their transmembrane receptors. Here we review recent findings from the Drosophila larval neuromuscular junction (NMJ) that illustrate how specific steps of intracellular traffic and inter-organelle interactions impinge on signaling, regulating synaptic growth and function. We also discuss how disease conditions may impact these signaling pathways by modulating membrane traffic.

    2. Actin, membrane trafficking and the control of prion induction, propagation and transmission in yeast

      Behrooz Moosavi, Bibimaryam Mousavi and Guang-Fu Yang

      Accepted manuscript online: 27 OCT 2015 05:56AM EST | DOI: 10.1111/tra.12344

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      Prion induction in yeast cells involves numerous proteins that, in alternate conformations, may play important roles in cellular processes such as endocytosis, protein trafficking, and protein-quality control. Actin patches act as the initial sites for the formation of prion aggregates, which are internalized and targeted to a protein quality control system to form an insoluble protein deposit (IPOD) and degradation by autophagy. Prion propagation, rather than degradation, occurs when molecular chaperones act prior to transport to and at the IPOD.

  5. Original Articles

    1. Endocytosis of ligand activated sphingosine 1-phosphate receptor 1 mediated by the clathrin-pathway

      Patrick M. Reeves, Yuan-Lin Kang and Tom Kirchhausen

      Accepted manuscript online: 20 OCT 2015 12:21AM EST | DOI: 10.1111/tra.12343

      We show here that the G protein–coupled receptor sphingosine 1-phosphate receptor 1 (S1PR1) activated by its natural lipid ligand S1P or the synthetic agonist FTY720P is rapidly internalized by the clathrin-dependent endocytic pathway. Depletion of activated S1PR1 from the cell surface relies on clathrin, its endocytic adaptor AP-2 dynamin and the non-visual βarrestin1 and βarrestin2, suggesting that activated S1PR1 is down-regulated from the cell surface using the canonical GPCR entry route.

    2. You have full text access to this OnlineOpen article
      VEGFR2 trafficking, signaling and proteolysis is regulated by the ubiquitin isopeptidase USP8

      Gina A. Smith, Gareth W. Fearnley, Izma A. Zani, Stephen B. Wheatcroft, Darren C. Tomlinson, Michael A. Harrison and Sreenivasan Ponnambalam

      Accepted manuscript online: 13 OCT 2015 02:17AM EST | DOI: 10.1111/tra.12341

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      Endothelial cells regulate many aspects of vascular physiology including blood pressure, vascular repair and new blood vessel sprouting. Binding of vascular endothelial growth factor A (VEGF-A) to a receptor tyrosine kinase (VEGFR2) stimulates intracellular signaling and the endothelial response. We show that the ubiquitin isopeptidase, USP8, is essential for VEGFR2 trafficking, de-ubiquitination, signal transduction and proteolysis. Biochemical pathways that control the ubiquitination and de-ubiquitination of VEGFR2 thus regulate endothelial decision-making processes that influence vascular physiology.


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