Dataset Information

The CD63-Syntenin-1 Complex Controls Post-Endocytic Trafficking of Oncogenic Human Papillomaviruses.

ABSTRACT: Human papillomaviruses enter host cells via a clathrin-independent endocytic pathway involving tetraspanin proteins. However, post-endocytic trafficking required for virus capsid disassembly remains unclear. Here we demonstrate that the early trafficking pathway of internalised HPV particles involves tetraspanin CD63, syntenin-1 and ESCRT-associated adaptor protein ALIX. Following internalisation, viral particles are found in CD63-positive endosomes recruiting syntenin-1, a CD63-interacting adaptor protein. Electron microscopy and immunofluorescence experiments indicate that the CD63-syntenin-1 complex controls delivery of internalised viral particles to multivesicular endosomes. Accordingly, infectivity of high-risk HPV types 16, 18 and 31 as well as disassembly and post-uncoating processing of viral particles was markedly suppressed in CD63 or syntenin-1 depleted cells. Our analyses also present the syntenin-1 interacting protein ALIX as critical for HPV infection and CD63-syntenin-1-ALIX complex formation as a prerequisite for intracellular transport enabling viral capsid disassembly. Thus, our results identify the CD63-syntenin-1-ALIX complex as a key regulatory component in post-endocytic HPV trafficking.

SUBMITTER: Graßel L

PROVIDER: S-EPMC5006017 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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The CD63-Syntenin-1 Complex Controls Post-Endocytic Trafficking of Oncogenic Human Papillomaviruses.

Gräßel Linda L Fast Laura Aline LA Scheffer Konstanze D KD Boukhallouk Fatima F Spoden Gilles A GA Tenzer Stefan S Boller Klaus K Bago Ruzica R Rajesh Sundaresan S Overduin Michael M Berditchevski Fedor F Florin Luise L

Scientific reports 20160831

Human papillomaviruses enter host cells via a clathrin-independent endocytic pathway involving tetraspanin proteins. However, post-endocytic trafficking required for virus capsid disassembly remains unclear. Here we demonstrate that the early trafficking pathway of internalised HPV particles involves tetraspanin CD63, syntenin-1 and ESCRT-associated adaptor protein ALIX. Following internalisation, viral particles are found in CD63-positive endosomes recruiting syntenin-1, a CD63-interacting adap ...[more]

PMID: 27578500

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Project description:Periodontal ligament contains periodontal ligament stem cells that maintain tissue homeostasis. Targeting hPDLSCs (human periodontal ligament cells) is a promising strategy for repair and regeneration of bone tissue destroyed by periodontal diseases. However, the mechanisms by which PDLSCs differentiate into osteoblasts to form a mineralized matrix is unclear. In this study, we demonstrate for the first time the molecular events that contribute to osteogenic differentiation of PDLSCs. Dentin matrix protein 1 (DMP1) and its receptor, Glucose regulated protein-78 (GRP78), are localized in the progenitor cells of the PDL. Our overall goal is to demonstrate the formation of DMP1-GRP78 complex at the plasma membrane and subsequent protein trafficking and nuclear localization to promote osteogenic differentiation. To study the internalization and routing of the complex, we mimic an in vivo differentiation scenario by stimulating cells with DMP1 and culturing them in the presence of osteogenic differentiation conditions. We first demonstrate the translocation of the ER chaperone protein GRP78 to the plasma membrane during the differentiation process. Total internal reflection microscopy imaging demonstrates the formation and internalization of the receptor- ligand (GRP78-DMP1) complex. Confocal microscopy results show the internalization of the GRP78-DMP1 complex specifically through the caveolin pathway and trafficked through the cell with various endocytic markers such as Rab5 and 7 GTPases to early and late endosomes respectively. DMP1 is ultimately transported to the nucleus where it functions to promote osteogenic differentiation as demonstrated by quantitative Real-Time PCR. This observation is the first report that suggests DMP1 and GRP78 can interact at the plasma membrane, then packaged in vesicles and ultimately DMP1 is routed to the nucleus where it aids in osteogenic differentiation of PDLSCs. Characterizing the osteogenic potential of PDLSCs would favor the development of therapeutic strategies for reconstruction of mineralized tissues destroyed by periodontal diseases.

Dataset Information

The CD63-Syntenin-1 Complex Controls Post-Endocytic Trafficking of Oncogenic Human Papillomaviruses.

Publications

The CD63-Syntenin-1 Complex Controls Post-Endocytic Trafficking of Oncogenic Human Papillomaviruses.

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