title: HIV-1 assembly differentially alters dynamics and partitioning of tetraspanins and raft components.
abstract: Partitioning of membrane proteins into various types of microdomains is crucial for many cellular functions. Tetraspanin-enriched microdomains (TEMs) are a unique type of protein-based microdomain, clearly distinct from membrane rafts, and important for several cellular processes such as fusion, migration and signaling. Paradoxically, HIV-1 assembly/egress occurs at TEMs, yet the viral particles also incorporate raft lipids. Using different quantitative microscopy approaches, we investigated the dynamic relationship between TEMs, membrane rafts and HIV-1 exit sites, focusing mainly on the tetraspanin CD9. Our results show that clustering of CD9 correlates with multimerization of the major viral structural component, Gag, at the plasma membrane. CD9 exhibited confined behavior and reduced lateral mobility at viral assembly sites, suggesting that Gag locally traps tetraspanins. In contrast, the raft lipid GM1 and the raft-associated protein CD55, while also recruited to assembly/budding sites, were only transiently trapped in these membrane areas. CD9 recruitment and confinement were found to be partially dependent on cholesterol, while those of CD55 were completely dependent on cholesterol. Importantly, our findings support the emerging concept that cellular and viral components, instead of clustering at preexisting microdomain platforms, direct the formation of distinct domains for the execution of specific functions.
authors: Graduate Program in Cell and Molecular Biology, University of Vermont, Burlington, VT 05405, USA.
authors: Dimitry N
authors: DN
authors: Krementsov
authors: Patrice
authors: P
authors: Rassam
authors: Emmanuel
authors: E
authors: Margeat
authors: Nathan H
authors: NH
authors: Roy
authors: Jürgen
authors: J
authors: Schneider-Schaulies
authors: Pierre-Emmanuel
authors: PE
authors: Milhiet
authors: Markus
authors: M
authors: Thali
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D036681:Fluorescence Recovery After Photobleaching; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism*; D014709:Vero Cells; D019065:Virus Assembly / Q000502:physiology*
chemical_list: D008562:Membrane Glycoproteins