Protein Secretion and Vesicle Traffic : Part 3: Human Diseases of Vesicle Budding (32:28)

What is the minimal set of cell-biological ingredients needed to generate a Golgi apparatus? The compositions of eukaryotic organelles arise through a process of molecular exchange via vesicle traffic. Here we statistically sample tens of thousands of homeostatic vesicle traffic networks generated by realistic molecular rules governing vesicle budding and fusion. Remarkably, the plurality of these networks contain chains of compartments that undergo creation, compositional maturation, and dissipation, coupled by molecular recycling along retrograde vesicles. This motif precisely matches the cisternal maturation model of the Golgi, which was developed to explain many observed aspects of the eukaryotic secretory pathway. In our analysis cisternal maturation is a robust consequence of vesicle traffic homeostasis, independent of the underlying details of molecular interactions or spatial stacking. This architecture may have been exapted rather than selected for its role in the secretion of large cargo.

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HOPS Interacts with Apl5 at the Vacuole Membrane and Is Required for Consumption of AP-3 Transport Vesicles

Molecular Biology of the Cell ◽

10.1091/mbc.e09-04-0272 ◽

2009 ◽

Vol 20 (21) ◽

pp. 4563-4574 ◽

Cited By ~ 52

Author(s):

Cortney G. Angers ◽

Alexey J. Merz

Keyword(s):

Fluorescence Microscopy ◽

Protein Complexes ◽

Adaptor Protein ◽

Vesicle Budding ◽

Vesicle Docking ◽

Vacuole Membrane ◽

Vesicle Traffic ◽

Transport Vesicles ◽

Evolutionarily Conserved ◽

Curved Membranes

Adaptor protein complexes (APs) are evolutionarily conserved heterotetramers that couple cargo selection to the formation of highly curved membranes during vesicle budding. In Saccharomyces cerevisiae , AP-3 mediates vesicle traffic from the late Golgi to the vacuolar lysosome. The HOPS subunit Vps41 is one of the few proteins reported to have a specific role in AP-3 traffic, yet its function remains undefined. We now show that although the AP-3 δ subunit, Apl5, binds Vps41 directly, this interaction occurs preferentially within the context of the HOPS docking complex. Fluorescence microscopy indicates that Vps41 and other HOPS subunits do not detectably colocalize with AP-3 at the late Golgi or on post-Golgi (Sec7-negative) vesicles. Vps41 and HOPS do, however, transiently colocalize with AP-3 vesicles when these vesicles dock at the vacuole membrane. In cells with mutations in HOPS subunits or the vacuole SNARE Vam3, AP-3 shifts from the cytosol to a membrane fraction. Fluorescence microscopy suggests that this fraction consists of post-Golgi AP-3 vesicles that have failed to dock or fuse at the vacuole membrane. We propose that AP-3 remains associated with budded vesicles, interacts with Vps41 and HOPS upon vesicle docking at the vacuole, and finally dissociates during docking or fusion.

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Paralogous gene modules derived from ancient hybridization drive vesicle traffic evolution in yeast

10.1101/2021.03.03.433305 ◽

2021 ◽

Author(s):

Ramya Purkanti ◽

Mukund Thattai

Keyword(s):

Paralogous Gene ◽

Endomembrane System ◽

Vesicle Budding ◽

Vesicle Traffic ◽

Selective Pressures ◽

Large Gene ◽

Hybridization Event ◽

Interspecies Hybridization ◽

Gene Modules ◽

Endocytic Pathways

AbstractModules of interacting proteins regulate vesicle budding and fusion in eukaryotes. Distinct paralogous copies of these modules act at distinct sub-cellular locations. The processes by which such large gene modules are duplicated and retained remain unclear. Here we show that interspecies hybridization is a potent source of paralogous gene modules. We study the dynamics of paralog doublets derived from the 100-million-year-old hybridization event that gave rise to the whole genome duplication clade of budding yeast. We show that paralog doublets encoding vesicle traffic proteins are convergently retained across species. Vesicle coats and adaptors involved in secretory and early-endocytic pathways are retained as doublets, while tethers and other machinery involved in intra-Golgi traffic and later endocytic steps are reduced to singletons. These patterns reveal common selective pressures that have sculpted traffic pathways in diverse yeast species. They suggest that hybridization may have played a pivotal role in the expansion of the endomembrane system.

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Experimental Amyloidosis Induced by Immune Complex

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100066978 ◽

1971 ◽

Vol 29 ◽

pp. 582-583

Author(s):

A. Kawaoi

Keyword(s):

Immune Complex ◽

Systemic Amyloidosis ◽

Human Diseases ◽

Experimental Amyloidosis ◽

Freund’S Complete Adjuvant ◽

Freund's Complete Adjuvant ◽

Immunological Approach ◽

Experimentally Induced

Numbers of immunological approach have been made to the amyloidosis through the variety of predisposing human diseases and the experimentally induced animals by the greater number of agents. The results suggest an important role of impaired immunity involving both humoral and cell-mediated aspects.Recently the author has succeeded in producing amyloidosis in the rabbits and mice by the injections of immune complex of heat denatured DNA.The aim of this report is to demonstrate the details of the ultrastructure of the amyloidosis induced by heterologous insoluble immune complex. Eleven of twelve mice, dd strain, subcutaneously injected twice a week with Freund's complete adjuvant and four of seven animals intraperitonially injected developed systemic amyloidosis two months later from the initial injections. The spleens were electron microscopically observed.

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