5 research outputs found
Retromer and Its Role in Regulating Signaling at Endosomes.
The retromer complex is a key element of the endosomal protein sorting machinery being involved in trafficking of proteins from endosomes to the Golgi and also endosomes to the cell surface. There is now accumulating evidence that retromer also has a prominent role in regulating the activity of many diverse signaling proteins that traffic through endosomes and this activity has profound implications for the functioning of many different cell and tissue types from neuronal cells to cells of the immune system to specialized polarized epithelial cells of the retina. In this review, the protein composition of the retromer complex will be described along with many of the accessory factors that facilitate retromer-mediated endosomal protein sorting to detail how retromer activity contributes to the regulation of several distinct signaling pathways
Supplementary Material for: The Janus Face of a-Toxin: A Potent Mediator of Cytoprotection in Staphylococci-Infected Macrophages
<p>After phagocytosis by macrophages, <i>Staphylococcus aureus</i>
evades killing in an a-toxin-dependent manner, and then prevents
apoptosis of infected cells by upregulating expression of antiapoptotic
genes like <i>MCL-1 (myeloid cell leukemia-1)</i>. Here, using purified a-toxin and a set of <i>hla</i>-deficient strains, we show that a-toxin is critical for the induction of <i>MCL-1 </i>expression
and the cytoprotection of infected macrophages. Extracellular or
intracellular treatment of macrophages with a-toxin alone did not induce
cytoprotection conferred by increased Mcl-1, suggesting that the
process is dependent on the production of a-toxin by intracellular
bacteria. The increased expression of <i>MCL-1</i> in infected cells was
associated with enhanced NFÎşB activation, and subsequent IL-6
secretion. This effect was only partially inhibited by blocking TLR2,
which suggests the participation of intracellular receptors in the
specific recognition of <i>S. aureus </i>strains secreting a-toxin. Thus, <i>S. aureus</i>
recognition by intracellular receptors and/or activation of downstream
pathways leading to Mcl-1 expression is facilitated by a-toxin released
by intracellular bacteria which permeabilize phagosomes, ensuring
pathogen access to the cytoplasmatic compartment. Given that the
intracellular survival of <i>S. aureus</i> depends on a-toxin, we
propose a novel role for this agent in the protection of the
intracellular niche, and further dissemination of staphylococci by
infected macrophages.</p