Cover image for Vol. 16 Issue 3

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

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. CD14, TLR4 and TRAM Show Different Trafficking Dynamics During LPS Stimulation

      Dionne C.G. Klein, Astrid Skjesol, Esther D. Kers-Rebel, Tatyana Sherstova, Bjørnar Sporsheim, Kjartan W. Egeberg, Bjørn T. Stokke, Terje Espevik and Harald Husebye

      Article first published online: 24 MAR 2015 | DOI: 10.1111/tra.12274

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      We have investigated the location and mobility of toll-like receptor 4 (TLR4) and its adaptor TRAM during lipopolysaccharide (LPS)-induced signaling and how RAB11A regulates TRAM trafficking. We show that LPS induces an immobile fraction of TLR4 in punctate structures containing CD14/LPS and clathrin. RAB11A drives TRAM into the endosomal recycling compartment (ERC) and onto early sorting endosomes. TRAM is recovered more from sorting endosomes than CD14/LPS. Our data suggest that RAB11A regulates LPS-induced interferon-β (IFN-β) production through its ability to transport TRAM form the Golgi to the ERC and further onto sorting endosomes.

    2. Lysosomal Targeting of Cystinosin Requires AP-3

      Zuzanna Andrzejewska, Nathalie Névo, Lucie Thomas, Anne Bailleux, Véronique Chauvet, Alexandre Benmerah and Corinne Antignac

      Article first published online: 24 MAR 2015 | DOI: 10.1111/tra.12277

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      Cystinosin, a seven transmembrane (TM) lysosomal cystine transporter defective in the autosomal recessive lysosomal storage disorder, has been shown to be targeted to lysosomes via two sorting signals: a tyrosine-based motif in its C-terminal (GYDQL) and a non-classical motif in its fifth inter-TM loop. Here, we show that the tyrosine-based motif specifically interacts with AP-3 complex and functions as a ‘strong’ AP-3 motif responsible for direct intracellular targeting of cystinosin and the CD63-cystinosin chimera (CD63-GYDQL) to late endosomes/lysosomes.

  2. Review Articles

    1. Organizing Polarized Delivery of Exosomes at Synapses

      Maria Mittelbrunn, Miguel Vicente-Manzanares and Francisco Sánchez-Madrid

      Article first published online: 3 MAR 2015 | DOI: 10.1111/tra.12258

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      Exosome secretion is a finely tuned mechanism of intercellular communication. Cellular orientation and polarized fusion of multivesicular bodies are central events in this process to enable efficacy and specificity. We offer an integrated perspective of the roles of the different cellular cytoskeletons, small GTPases and phospholipid signaling circuits that drive the polarization of MVBs toward specific points of the plasma membrane and its function in crucial physiological processes including immune and neuronal synapses, cell migration and the function of epithelial sheets.

  3. Corrigendum

    1. You have free access to this content
      The RAB5-GEF Function of RIN1 Regulates Multiple Steps During Listeria monocytogenes Infection

      Kavitha Balaji, Christopher T. French, Jeff F. Miller and John Colicelli

      Article first published online: 24 FEB 2015 | DOI: 10.1111/tra.12268

      This article corrects:

      The RAB5-GEF Function of RIN1 Regulates Multiple Steps During Listeria monocytogenes Infection

      Vol. 15, Issue 11, 1206–1218, Article first published online: 4 SEP 2014

  4. Original Articles

    1. New Export Pathway in Plasmodium falciparum-Infected Erythrocytes: Role of the Parasite Group II Chaperonin, PfTRiC

      Alassane Mbengue, Emilie Vialla, Laurence Berry, Gamou Fall, Nicolas Audiger, Edith Demettre-Verceil, David Boteller and Catherine Braun-Breton

      Article first published online: 24 FEB 2015 | DOI: 10.1111/tra.12266

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      The malaria parasite type II chaperonin PfTRiC is exported to the host erythrocyte cytoplasm and translocates unfolded parasite proteins from the parasitophorous vacuole to the membrane of Maurer's clefts. Since some of these exported proteins have the PEXEL export signature, the PfTRiC cargos likely use the PTEX translocon to pass through the parasitophorous vacuole membrane. Detection of PfTRiC in the parasitophorous vacuole lumen suggests a role for this chaperonin in the export of parasite proteins through different compartments.

    2. Disease-Associated Mutations of TREM2 Alter the Processing of N-Linked Oligosaccharides in the Golgi Apparatus

      Ji-Seon Park, In Jung Ji, Hyun Joo An, Min-Ji Kang, Sang-Wook Kang, Dong-Hou Kim and Seung-Yong Yoon

      Article first published online: 24 FEB 2015 | DOI: 10.1111/tra.12264

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      Model for trafficking and glycosylation of wild-type and mutant triggering receptor expressed on myeloid cells (TREM2). Wild-type TREM2 is normally trafficked and glycosylated from endoplasmic reticulum (ER) to Golgi and plasma membrane. However, Y38C or T66M mutant TREM2 is impaired in this process and accumulated in the ER to induce ER stress. R47H TREM2 is glycosylated differently from the wild type in the Golgi.

    3. Effect of Clathrin Light Chains on the Stiffness of Clathrin Lattices and Membrane Budding

      Philip N. Dannhauser, Mitja Platen, Heike Böning, Huberta Ungewickell, Iwan A.T. Schaap and Ernst J. Ungewickell

      Article first published online: 24 FEB 2015 | DOI: 10.1111/tra.12263

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      Clathrin lattices were constructed on rigid planar, convex and concave surfaces. Convex surfaces were the preferred substrate, but lattices can also form on planar and on weakly concave surfaces. The uncoating protein Hsc70 disrupts both, convex and planar clathrin lattices. Atomic force microscopy of planar clathrin lattices demonstrated that the lattices are ∼12 nm high as opposed to 6 nm in the absence of light chains. Moreover, it is shown that light chains affect the membrane bending efficiency of clathrin.

    4. Granule Mobility, Fusion Frequency and Insulin Secretion Are Differentially Affected by Insulinotropic Stimuli

      Kirstin Schumacher, Magnus Matz, Dennis Brüning, Knut Baumann and Ingo Rustenbeck

      Article first published online: 24 FEB 2015 | DOI: 10.1111/tra.12261

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      The arrival of insulin granules at and departure from the plasma membrane is increased by glucose and high K+, accelerating the turnover. The number of granules remaining at the membrane decreases exponentially with time. The mobility pattern suggests that the majority of fusing granules is derived from long-term resident granules, but a highly mobile fast-fusing subgroup also exists. Increased cytosolic calcium affects fusion, but is not necessary for increased turnover. The actual secretion is additionally shaped by the heterogeneity of the post-fusion fate of the granules and (possibly) oscillatory regulation of fusion.

    5. A Second Las17 Monomeric Actin-Binding Motif Functions in Arp2/3-Dependent Actin Polymerization During Endocytosis

      Daniel Feliciano, Thomas O. Tolsma, Kristen B. Farrell, Al Aradi and Santiago M. Di Pietro

      Article first published online: 24 FEB 2015 | DOI: 10.1111/tra.12259

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      Actin polymerization driven by the Arp2/3 complex is essential for endocytosis. A second monomeric actin-binding site, LGM, was mapped in Las17, the strongest activator of the Arp2/3 complex. LGM was characterized in vitro utilizing the yeast two-hybrid system, GST-pulldown, fluorescence polarization and pyrene-actin polymerization assays. The functional importance of LGM was established in vivo by analyzing the dynamics of actin polymerization, other components of the endocytic machinery and cargo internalization by live-cell fluorescence microscopy.

    6. Molecular Control of B Cell Activation and Immunological Synapse Formation

      Elina Kuokkanen, Vid Šuštar and Pieta K Mattila

      Article first published online: 20 FEB 2015 | DOI: 10.1111/tra.12257

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      This review article discusses how B cells are activated upon recognition of antigens on the surface of antigen-presenting cells via the formation of so-called immunological synapse, a specialized cell–cell interface. The molecular mechanisms and the multiplex role of the actin cytoskeleton are highlighted.

    7. Atg27 Tyrosine Sorting Motif is Important for Its Trafficking and Atg9 Localization

      Verónica A. Segarra, Douglas R. Boettner and Sandra K. Lemmon

      Article first published online: 20 FEB 2015 | DOI: 10.1111/tra.12253

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      The transmembrane protein Atg27 facilitates transport of the major autophagy membrane protein, Atg9, to the preautophagosomal structure (PAS). This new study demonstrates that Atg27 has a tyrosine-sorting motif in its cytoplasmic tail that mediates its localization to the vacuole membrane by the AP-3 adaptor pathway. Moreover, this motif is also important for preventing Atg9 delivery to the vacuole lumen via the MVB pathway, suggesting that Atg27 retains Atg9 in endosomal reservoirs for mobilization during autophagy.


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