Trafficking of Varicella-Zoster Virus Glycoprotein gI: T 338 -Dependent Retention in the trans -Golgi Network, Secretion, and Mannose 6-Phosphate-Inhibitable Uptake of the Ectodomain
| العنوان: | Trafficking of Varicella-Zoster Virus Glycoprotein gI: T 338 -Dependent Retention in the trans -Golgi Network, Secretion, and Mannose 6-Phosphate-Inhibitable Uptake of the Ectodomain |
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| المؤلفون: | Zhenglun Zhu, Octavian Lungu, Zuo-Hong Wang, Anne A. Gershon, Michael D. Gershon |
| المصدر: | Journal of Virology. 74:6600-6613 |
| بيانات النشر: | American Society for Microbiology, 2000. |
| سنة النشر: | 2000 |
| مصطلحات موضوعية: | Herpesvirus 3, Human, Endosome, Recombinant Fusion Proteins, Molecular Sequence Data, Immunology, Endocytic cycle, Fluorescent Antibody Technique, Golgi Apparatus, Endosomes, Biology, Endocytosis, Microbiology, symbols.namesake, Viral Envelope Proteins, Sequence Analysis, Protein, Virology, parasitic diseases, Animals, Humans, Amino Acid Sequence, Mannosephosphates, Endoplasmic reticulum, Cell Membrane, Peripheral membrane protein, Transport vesicle membrane, Biological Transport, Receptors, Interleukin-2, social sciences, Golgi apparatus, Virus-Cell Interactions, Protein Structure, Tertiary, Cell biology, Amino Acid Substitution, Ectodomain, Biochemistry, Insect Science, COS Cells, Mutation, symbols, population characteristics, human activities, geographic locations |
| الوصف: | Envelopment of varicella-zoster virus (VZV) has been proposed to be a two-step process that is completed in the trans-Golgi networks (TGN) of infected cells (8). According to this hypothesis, nucleocapsids assemble in the nucleus and acquire a primary envelope by budding through the inner nuclear membrane. Budding delivers the temporarily enveloped virions to the perinuclear cisterna, which is continuous with the rough endoplasmic reticulum (RER). Fusion of the primary envelope with the membranes of the RER enables the nucleocapsids to gain access to the cytosol, though which they are translocated to the TGN. The VZV glycoproteins (gps) are synthesized on attached polyribosomes and are transported as integral or peripheral membrane proteins from the RER via the Golgi apparatus to the TGN, where they are concentrated for incorporation into the final viral envelope. Tegument proteins lack signal sequences (6) and must thus be synthesized on free polyribosomes in the cytosol; nevertheless, there is evidence that tegument proteins that are included in assembled virions also concentrate in the region of the TGN, where they are associated with the cytosolic domains (endodomains) of integral membrane gps (8). Envelopment within the TGN is thought to involve the restriction of gps to the concave surface of flattened sacs that wrap around nucleocapsids (Fig. (Fig.1).1). Tegument is trapped by the wrapping process and so becomes included in the final virion. A process of fusion of membranes with subsequent fission converts the enveloping sac into an inner viral envelope and an outer transport vesicle. In cells that contain a lysosomal pathway, the transport vesicle membrane is rich in the large cation-independent mannose 6-phosphate receptor (MPR). Perhaps for this reason, virions are directed in tissue culture cells to acidic post-Golgi vacuoles that have been identified as late endosomes (7, 8). Virions appear to be inactivated in these vacuoles, accounting for the strict cell association of VZV when propagated in tissue culture. FIG. 1 Heuristic model depicting the envelopment of VZV. Viral gps are synthesized in the RER and transported through the cis-Golgi network (CGN) and Golgi stack to the TGN, where they concentrate. Step 1: curvilinear vacuoles appear in the TGN. Tegument is ... The hypothesis that the final site of VZV envelopment is the TGN requires that all of the components of the final virion be targeted to this organelle. For the integral membrane gps, targeting could involve signal sequences or patches in the primary structure of the proteins. Alternatively, gps that lack such targeting information (passenger gps) could still be sorted to the TGN if they were to form complexes with gps that do contain targeting sequences (navigator gps). Previous data has indicated that gE, the most abundant gp of VZV (9), is targeted to the TGN as a result of the presence in its endodomain of a targeting sequence, AYRV, and a signal patch rich in acidic amino acids (2, 46). These signaling regions resemble those which have been found in the endodomains of the endogenous TGN proteins furin (12, 39) and TGN38 (3, 11, 25, 27, 38, 40). The targeting of gE to the TGN is an indirect process that includes its endocytosis from the plasma membrane, followed by selective retrieval to the TGN (2, 45). In keeping with this route of transport, there is an endocytosis signal in the endodomain of gE (21). The mechanism by which gI is concentrated in the TGN is less clear than that for gE. Since the N-terminal domain of gI forms a complex with gE in the RER (14, 42), gI might be expected to be simply a passenger gp and follow the itinerary navigated by gE. If this were to be the case, then gI would not be targeted to the TGN in transfected cells that express gI by itself. Targeting of gI to the TGN would only occur in cells that express both gI and gE. There is evidence that gI is recycled from the plasma membrane by endocytosis when it is expressed by itself in HeLa cells (19); however, a contrary study reports that HeLa cells that express gI restrict it to the plasma membrane and do not reinternalize gI (1). This latter report also maintains that gI is not targeted to the TGN unless it is coexpressed in HeLa cells together with gE. In contrast, gI has been found to be targeted to the TGN when expressed by itself in transfected Cos-7 cells (36). Conceivably, foreign proteins could be transported differently in different types of cell. To be transported, a foreign protein would have to contain a signaling domain, but the cell would also have to express an endogenous receptor capable of responding to the signal sequence or patch in the protein. The successful targeting of gI to the TGN of Cos-7 cells indicates that TGN targeting information is present in the primary sequence of gI, which can be recognized by at least some types of cell. That phenomenon is significant, because there is no reason to believe that Cos-7 cells are unique. The cellular machinery that enables Cos-7 cells to respond to signaling information in the primary sequence of gI is thus likely also to be present in additional cell types. The current experiments were undertaken to identify and characterize the signaling domain that is responsible for the ability of Cos-7 cells to target gI to the TGN. An additional goal was to compare the routes to the TGN followed by transported gI and gE. Because gI and gE form a complex (13, 41, 42), the sorting of these proteins was analyzed in cells in which they were expressed individually and also in those in which they were coexpressed. The data confirm that gI is targeted to the TGN when expressed by itself in Cos-7 cells, the responsible targeting signal resides in the endodomain of gI, and T338 is critical for targeting. In contrast to gE, the independent targeting of gI does not involve retrieval from the plasma membrane but retention of gI in the TGN during intracellular transport. Truncation of the C-terminal domain of gI, including the transmembrane region, causes the mutant protein to be secreted. Nontransfected cells take up the secreted protein by an endocytic mechanism that is inhibited by mannose 6-phosphate (Man 6-P). |
| تدمد: | 1098-5514 0022-538X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f17b6cae6ffa99fe67c3e17807488fc8Test https://doi.org/10.1128/jvi.74.14.6600-6613.2000Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f17b6cae6ffa99fe67c3e17807488fc8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10985514 0022538X |
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