© John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Edited By: Michael S. Marks, Trina A. Schroer, Tom H. Stevens and Sharon A. Tooze
Online ISSN: 1600-0854
Recently Published Articles
- 14-3-3 Proteins regulate K2P5.1 surface expression on T lymphocytes
Juncal Fernández-Orth, Petra Ehling, Tobias Ruck, Susann Pankratz, Majella-Sophie Hofmann, Peter Landgraf, Daniela C. Dieterich, Karl-Heinz Smalla, Thilo Kähne, Guiscard Seebohm, Thomas Budde, Heinz Wiendl, Stefan Bittner and Sven G. Meuth
Version of Record online: 27 NOV 2016 | DOI: 10.1111/tra.12455
K2P5.1 channels possess a putative non-classical consensus motif for 14-3-3 proteins that mediates the interaction and promotes K2P5.1 channels to the plasma membrane. An amino acid mutation reduces the binding of 14-3-3 proteins to K2P5.1 resulting in a reduced number of channels at the plasma membrane and a decreased potassium efflux. Pharmacological inhibition of 14-3-3 protein binding to K2P5.1 functionally impacts T-cell proliferation and cytokine production. 14-3-3 proteins may represent a pharmacological target for the treatment of multiple sclerosis and other autoimmune diseases.
- Cargo Selectivity of Yeast Sorting Nexins
Björn D.M. Bean, Michael Davey and Elizabeth Conibear
Accepted manuscript online: 24 NOV 2016 10:25AM EST | DOI: 10.1111/tra.12459
Yeast sorting nexins direct membrane proteins on different endosomal trafficking pathways, but the number of known cargos is limited, and few sorting signals have been defined. Here, we used a large scale imaging screen to find 23 new sorting nexin cargo proteins, and identified cytosolic sequences that are necessary for sorting nexin-dependent localization and endosomal recycling. This allowed us to define a consensus sequence for Snx3 and retromer-dependent cargo sorting.
- Microbe-inducible trafficking pathways that control Toll-like receptor signaling
Yunhao Tan and Jonathan C. Kagan
Version of Record online: 23 NOV 2016 | DOI: 10.1111/tra.12454
In the context of lipopolysaccharide (LPS) stimulation, CD14 and MD-2 serve as Transporters Associated with the eXecution of Inflammation (TAXI) proteins for Toll-like receptors 4 (TLR4) to trigger plasma membrane myddosome formation and induce proinflammatory cytokine production. Subsequent endocytosis of TLR4 activates the TRAM and TRIF-dependent signaling process leading to type I IFN production. Intracellular TLR4 signaling could occur at distinct compartments including endosomes, multivesicular bodies (MVBs), phagosomes. Ubiquitinylation and hepatocyte growth factor regulated tyrosine kinase substrate (HRS)-mediated sorting processes have been implicated in the intracellular sorting of TLR4. In the context of lipotechoic acids (LTA) stimulation, MBL functions as a TAXI protein for the TLR2/6 heterodimer. MBL delivers LTA to the phagosome where a TLR2/6 heterodimer may promote myddosome formation to induce proinflammatory cytokine production.
- Cellular and viral peptides bind multiple sites on the N-terminal domain of clathrin
Julia Muenzner, Linton M. Traub, Bernard T. Kelly and Stephen C. Graham
Accepted manuscript online: 3 NOV 2016 09:07PM EST | DOI: 10.1111/tra.12457
Linear peptide motifs of adaptor proteins recruit clathrin to membranes via interactions with the clathrin heavy chain N-terminal domain (NTD), a critical step in post-Golgi membrane trafficking. We present structures of NTD bound to cellular and viral clathrin-binding peptide motifs, which unexpectedly all bind to multiple sites on NTD. Biochemical analysis confirms that multiple binding sites are required for efficient capture of NTD by adaptor peptides. Our crystallographic studies also structurally define the proposed ‘fourth’ peptide binding site on NTD.