Complex polarity: building multicellular tissues through apical membrane traffic
Abstract
The formation of distinct subdomains of the cell surface is crucial for multicellular organism development. The most striking example of this is apical‐basal polarization. What is much less appreciated is that underpinning an asymmetric cell surface is an equally dramatic intracellular endosome rearrangement. Here, we review the interplay between classical cell polarity proteins and membrane trafficking pathways, and discuss how this marriage gives rise to cell polarization. We focus on those mechanisms that regulate apical polarization, as this is providing a number of insights into how membrane traffic and pol...
Source: Traffic - May 31, 2016 Category: Research Authors: Alvaro Roman‐Fernandez, David M. Bryant Tags: Review Source Type: research
A Genetic Screen Identifies a Critical Role for the WDR81 ‐WDR91 Complex in the Trafficking and Degradation of Tetherin
Tetherin (BST2/CD317) is a viral restriction factor that anchors enveloped viruses to host cells and limits viral spread. The HIV‐1 Vpu accessory protein counteracts tetherin by decreasing its cell surface expression and targeting it for ubiquitin‐dependent endolysosomal degradation. Although the Vpu‐mediated downregulation of tetherin has been extensively studied, the molecular details are not completely elucidated. We therefore used a forward genetic screen in human haploid KBM7 cells to identify novel genes required for tetherin trafficking. Our screen identified WDR81 as a novel gene required for tetherin traffic...
Source: Traffic - May 24, 2016 Category: Research Authors: Radu Rapiteanu, Luther J. Davis, James C. Williamson, Richard T. Timms, J. Paul Luzio, Paul J. Lehner Tags: Original Article Source Type: research
Alphavirus restriction by IFITM proteins
Abstract
Interferon inducible transmembrane proteins (IFITMs) are broad‐spectrum antiviral factors. In cell culture the entry of many enveloped viruses, including orthomyxo‐, flavi‐, and filoviruses, is inhibited by IFITMs, though the mechanism(s) involved remain unclear and may vary between viruses. We demonstrate that Sindbis and Semliki Forest virus (SFV), which both use endocytosis and acid‐induced membrane fusion in early endosomes to infect cells, are restricted by the early endosomal IFITM3. The late endosomal IFITM2 is less restrictive and the plasma membrane IFITM1 does not inhibit normal infection by eith...
Source: Traffic - May 24, 2016 Category: Research Authors: Stuart Weston, Stephanie Czieso, Ian J. White, Sarah E. Smith, Rachael S. Wash, Carmen Diaz‐Soria, Paul Kellam, Mark Marsh Tags: Original Article Source Type: research
Distinct roles for APPL1 and APPL2 in regulating Toll‐like receptor 4 signaling in macrophages
Abstract
Macrophages are activated by contact with pathogens to mount innate immune defenses against infection. Toll‐like receptor 4 (TLR4) at the macrophage surface recognizes and binds bacterial lipopolysaccharide (LPS), setting off signaling and transcriptional events that lead to the secretion of pro‐ and anti‐inflammatory cytokines; these in turn control inflammatory and antimicrobial responses. Although the complex regulatory pathways downstream of TLR4 have been extensively studied, further molecules critical for modulating the resulting cytokine outputs remain to be characterized. Here we establish potentia...
Source: Traffic - May 23, 2016 Category: Research Authors: Jeremy C. Yeo, Adam A. Wall, Lin Luo, Nicholas D. Condon, Jennifer L. Stow Tags: Original Article Source Type: research
Use of BODIPY‐cholesterol (TF‐Chol) for visualizing lysosomal cholesterol accumulation
Abstract
BODIPY‐cholesterol (TopFluor‐Cholesterol, TF‐Chol) is a widely used cholesterol analogue due to its excellent fluorescence properties and considerable similarity with natural cholesterol in terms of membrane partitioning. However, the suitability of TF‐Chol for detecting lysosomal cholesterol deposition has recently been questioned. Here, we highlight the fact that the method of lipid delivery and the analysis time point both affect the membrane distribution and labeling pattern of TF‐Chol, similarly as with radiolabeled cholesterol. Lysosomal sterol accumulation characteristic to a lysosomal storage dis...
Source: Traffic - May 18, 2016 Category: Research Authors: Maarit Hölttä‐Vuori, Erdinc Sezgin, Christian Eggeling, Elina Ikonen Tags: Traffic Interchange Source Type: research
