Comparison of the intracellular pathways of transferrin recycling and vesicular stomatitis virus membrane glycoprotein exocytosis by ultrastructural double-label cytochemistry.

Hedman, Klaus; Goldenthal, Karen L.; Rutherford, Angelina V.; Pastan, Ira

doi:10.1177/35.2.3025294

Cited by 25 publications

(20 citation statements)

References 46 publications

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“…It cannot be answered, whether components of the biosynthetic system possibly fuse with and become integrated into the endocytic networks and the endocytic TGN also functions in the secretory system. Compartments containing both endocytic and biosynthetic molecules have been demonstrated repeatedly at the trans Golgi side and it is well known that there are multiple interactions between endocytic and biosynthetic systems (see, for example, Fishman and Fine 1987;Hedman et al 1987;Pavelka et al 1998;Stoorvogel et al 1988;Volz et al 1995; for review see Farquhar and Hauri 1997). Current studies concentrate on the question, whether the prominent endocytic TGNs shown here correspond to common endocytic secretory compartments.…”

Section: Discussionmentioning

confidence: 92%

Golgi apparatus and TGN during endocytosis

Vetterlein

Ellinger

Neumüller

et al. 2002

Histochem Cell Biol

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Wheat germ agglutinin labelled with horseradish peroxidase (WGA) was used for analyses of endosomal compartments and Golgi apparatus in HepG(2) hepatoma cells during early and late periods of endocytosis. WGA was rapidly transferred into the Golgi region. Transport of internalised WGA into the Golgi apparatus could be classified in three stages. A short stage I, characterised by predominance of vesicular endosomes, was followed by stage II showing new formations of extended endocytic trans Golgi networks (TGNs); the endocytic TGNs comprised reticular and globular parts, showed intimate associations with segments of the endoplasmic reticulum and budding of multiple coated vesicles. Parts of the endocytic TGNs associated with trans Golgi cisternae and became integrated into Golgi stacks. During stage III, concomitantly with integration into the stacks, the endocytic TGNs decreased in size and stacked Golgi cisternae became prominent endocytic compartments. Our results show that endocytosis of WGA is connected with extensive membrane dynamics at the trans Golgi side: an endocytic TGN is newly formed, increases in size and is consumed again. The findings suggest that incorporation of TGN elements into Golgi stacks provides a mechanism for uptake of internalised WGA into the Golgi apparatus.

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Section: Discussionmentioning

confidence: 92%

Golgi apparatus and TGN during endocytosis

Vetterlein

Ellinger

Neumüller

et al. 2002

Histochem Cell Biol

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“…All enveloped viruses have hijacked this system to deliver their glycoproteins to the correct membranes to envelop their capsid structures (52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63). In at least one instance, the Nipah virus F protein requires endocytic recycling to activate its F protein in the late endosome/lysosome by either cathepsin B or cathepsin L (26,64,65).…”

Section: Discussionmentioning

confidence: 99%

Preventing Cleavage of the Respiratory Syncytial Virus Attachment Protein in Vero Cells Rescues the Infectivity of Progeny Virus for Primary Human Airway Cultures

Corry

Johnson

Cornwell

et al. 2016

J Virol

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All live attenuated respiratory syncytial virus (RSV) vaccines that have advanced to clinical trials have been produced in Vero cells. The attachment (G) glycoprotein in virions produced in these cells is smaller than that produced in other immortalized cells due to cleavage. These virions are 5-fold less infectious for primary well-differentiated human airway epithelial (HAE) cell cultures. Because HAE cells are isolated directly from human airways, Vero cell-grown vaccine virus would very likely be similarly inefficient at initiating infection of the nasal epithelium following vaccination, and therefore, a larger inoculum would be required for effective vaccination. We hypothesized that Vero cell-derived virus containing an intact G protein would be more infectious for HAE cell cultures. Using protease inhibitors with increasing specificity, we identified cathepsin L to be the protease responsible for cleavage. Our evidence suggests that cleavage occurs in the late endosome or lysosome during endocytic recycling. Cathepsin L activity was 100-fold greater in Vero cells than in HeLa cells. In addition, cathepsin L was able to cleave the G protein in Vero cell-grown virions but not in HeLa cell-grown virions, suggesting a difference in G-protein posttranslational modification in the two cell lines. We identified by mutagenesis amino acids important for cleavage, and these amino acids included a likely cathepsin L cleavage site. Virus containing a modified, noncleavable G protein produced in Vero cells was 5-fold more infectious for HAE cells in culture, confirming our hypothesis and indicating the value of including such a mutation in future live attenuated RSV vaccines. IMPORTANCEWorldwide, RSV is the second leading infectious cause of infant death, but no vaccine is available. Experimental live attenuated RSV vaccines are grown in Vero cells, but during production the virion attachment (G) glycoprotein is cleaved. Virions containing a cleaved G protein are less infectious for primary airway epithelial cells, the natural RSV target. In the study described here we identified the protease responsible, located the cleavage site, and demonstrated that cleavage likely occurs during endocytic recycling. Moreover, we showed that the infectivity of Vero cell-derived virus for primary airway epithelial cells is increased 5-fold if the virus contains a mutation in the G protein that prevents cleavage. The blocking of cleavage should improve RSV vaccine yield, consequently reducing production costs. Posttranslational cleavage of the fusion glycoprotein of many viruses plays an essential role in activation; however, cleavage of the RSV G protein is a novel example of a detrimental effect of cleavage on virus infectivity. In adults and teenagers, most respiratory syncytial virus (RSV) infections produce upper respiratory tract infection and symptoms. However, in infants, the immunocompromised, and the elderly, RSV has the potential to cause life-threatening lower respiratory tract infection (1-4). Worldwide, in 2010 ...

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“…Endosome-TGN communication has been implicated in retrograde transport of protein toxins and the cycling of transport machinery (e.g., the endopeptidase furin; Sandvig and van Deurs, 2002;Bonifacino and Rojas, 2006). Moreover, the endosomal system-in particular the endocytic recycling compartment (ERC), a pericentrosomal organelle with complex sorting functions (Maxfield and McGraw, 2004)-is emerging as an intermediate in biosynthetic transport to the PM (Hedman et al, 1987;Futter et al, 1995;Leitinger et al, 1995;Orzech et al, 2000;Harsay and Schekman, 2002;Yoo et al, 2002;Ang et al, 2004;Lock and Stow, 2005;Gravotta et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…Brefeldin A (BFA), a drug that dissociates coat proteins (COPs) from IC/cis-Golgi (COPI) and TGN/endosomes (clathrin and adaptor proteins), revealed a functional division of the Golgi apparatus. During the ensuing MTdependent Golgi disassembly cis-, medial-, and trans-Golgi compartments merge with the ER (Klausner et al, 1992), whereas the TGN-as defined by TGN38 and the mannose-6-phosphate receptor that binds lysosomal enzymes-seems to fuse with an endosomal network that converges around the centrosome ( et al, 1987;Futter et al, 1995;Leitinger et al, 1995;Orzech et al, 2000;Harsay and Schekman, 2002;Yoo et al, 2002;Ang et al, 2004;Lock and Stow, 2005;Gravotta et al, 2007). Assuming continuous, vectorial flow of membranes toward the TGN, the IC elements operating at the ER-Golgi boundary could be seen as pleiomorphic transport carriers, which after their arrival in the Golgi region transform into or fuse with the cis-Golgi cisternae (Glick et al, 1997;Bannykh et al, 1998;Lippincott-Schwartz et al, 2000).…”

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confidence: 99%

The Function of the Intermediate Compartment in Pre-Golgi Trafficking Involves its Stable Connection with the Centrosome

Marie

Dale

Sannerud

et al. 2009

MBoC

125

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Because the functional borders of the intermediate compartment (IC) are not well defined, the spatial map of the transport machineries operating between the endoplasmic reticulum (ER) and the Golgi apparatus remains incomplete. Our previous studies showed that the IC consists of interconnected vacuolar and tubular parts with specific roles in pre-Golgi trafficking. Here, using live cell imaging, we demonstrate that the tubules containing the GTPase Rab1A create a long-lived membrane compartment around the centrosome. Separation of this pericentrosomal domain of the IC from the Golgi ribbon, due to centrosome motility, revealed that it contains a distinct pool of COPI coats and acts as a temperaturesensitive way station in post-ER trafficking. However, unlike the Golgi, the pericentrosomal IC resists the disassembly of COPI coats by brefeldin A, maintaining its juxtaposition with the endocytic recycling compartment, and operation as the focal point of a dynamic tubular network that extends to the cell periphery. These results provide novel insight into the compartmental organization of the secretory pathway and Golgi biogenesis. Moreover, they reveal a direct functional connection between the IC and the endosomal system, which evidently contributes to unconventional transport of the cystic fibrosis transmembrane conductance regulator to the cell surface. INTRODUCTIONThe biosynthetic-secretory pathway sorts and delivers newly synthesized proteins and lipids, many with attached glycans, to the various endomembrane compartments of the cell and to its exterior (Palade, 1982). The dynamics and spatial organization of the secretory compartments-endoplasmic reticulum (ER), intermediate compartment (IC), and Golgi apparatus-depend on the microtubule (MT) and actin cytoskeleton and associated motor proteins (Thyberg and Moskalewski, 1999;Lippincott-Schwartz et al., 2000;Allan et al., 2002;Egea et al., 2006). The prevailing paradigm of the secretory pathway in mammalian cells states that the Golgi apparatus, positioned around the MT-organizing center (MTOC)/centrosome (Rios and Bornens, 2003), receives nascent proteins from widely distributed ER exit sites (ERES) due to MT-dependent centralization of IC elements (Saraste and Svensson, 1991;Bannykh et al., 1996;Presley et al., 1997;Scales et al., 1997;Hammond and Glick, 2000). After their post-translational modification and sorting in the Golgi, the proteins are distributed to the endolysosomal system, secretory granules, and the plasma membrane (PM;De Matteis and Luini, 2008). This spatial arrangement of the secretory process, consisting of centripetal and centrifugal transfer of biosynthetic products, is not essential for transport as such (Thyberg and Moskalewski, 1999;Hawes et al., 2008). However, it can promote the coalignment of the secretory and endocytic routes, allowing their communication at multiple sites (Saraste and Kuismanen, 1992;Bonifacino and Rojas, 2006) and facilitate the processing and sorting of cargo along these pathways via the establishment of a lume...

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Comparison of the intracellular pathways of transferrin recycling and vesicular stomatitis virus membrane glycoprotein exocytosis by ultrastructural double-label cytochemistry.

Abstract: Golgi stacks and vacuolar, tubular, vesicular, and pit-like structures of the Golgi system. A transferrin-ferri-I Supported by the Thanks to Scandinavia Foundation and by Virustautien tutkimuksen Kannatusyhdistys. KH is a Fogarty International Fellow.

Cited by 25 publications

References 46 publications

Golgi apparatus and TGN during endocytosis

Golgi apparatus and TGN during endocytosis

Preventing Cleavage of the Respiratory Syncytial Virus Attachment Protein in Vero Cells Rescues the Infectivity of Progeny Virus for Primary Human Airway Cultures

The Function of the Intermediate Compartment in Pre-Golgi Trafficking Involves its Stable Connection with the Centrosome

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