3 research outputs found
Mammalian Atg8 proteins regulate lysosome and autolysosome biogenesis through SNAREs
Mammalian homologs of the yeast Atg8 protein (mAtg8s) are important in
autophagy, but their exact mode of action remains to be defined. Recently,
syntaxin 17 (Stx17), a SNARE with major roles in autophagy, was shown to bind
mAtg8s. Here we broadened the analysis of potential mAtg8-SNARE interactions
and identified LC3-interacting regions (LIRs) in several SNAREs. Syntaxin 16
(Stx16), and its cognate SNARE partners all have LIR motifs and bind mAtg8s. A
knockout in STX16 caused defects in lysosome biogenesis whereas a double
STX16 and STX17 knockout completely blocked autophagic flux and decreased
mitophagy, pexophagy, xenophagy, and ribophagy. Mechanistic analyses
revealed that mAtg8s and Stx16 maintained several aspects of lysosomal
compartments including their functionality as platforms for active mTOR. These
findings reveal a broad direct interaction of mAtg8s with SNAREs with impact on
membrane remodeling in eukaryotic cells and expand the roles of mAtg8s to
lysosome biogenesis.</p
Synthetic Nanoparticles for Vaccines and Immunotherapy
The immune system plays a critical role in our health. No other component of human physiology plays a decisive role in as diverse an array of maladies, from deadly diseases with which we are all familiar to equally terrible esoteric conditions: HIV, malaria, pneumococcal and influenza infections; cancer; atherosclerosis; autoimmune diseases such
as lupus, diabetes, and multiple sclerosis. The importance of understanding the function of the immune system and learning how to modulate immunity to protect against or treat disease thus cannot be overstated. Fortunately, we are entering an exciting era where the
science of immunology is defining pathways for the rational manipulation of the immune system at the cellular and molecular level, and this understanding is leading to dramatic advances in the clinic that are transforming the future of medicine.1,2 These initial advances are being made primarily through biologic drugs– recombinant proteins (especially antibodies) or patient-derived cell therapies– but exciting data from preclinical studies suggest that a marriage of approaches based in biotechnology with the materials science and chemistry of nanomaterials, especially nanoparticles, could enable more effective and safer immune engineering strategies. This review will examine these nanoparticle-based strategies to immune modulation in detail, and discuss the promise and outstanding challenges facing the field of immune engineering from a chemical biology/materials engineering perspectiveNational Institutes of Health (U.S.) (Grants AI111860, CA174795, CA172164, AI091693, and AI095109)United States. Department of Defense (W911NF-13-D-0001 and Awards W911NF-07-D-0004