Mapping of tetraspanin-enriched microdomains that can function as gateways for HIV-1.
Specific spatial arrangements of proteins and lipids are central to the coordination of many biological processes. Tetraspanins have been proposed to laterally organize cellular membranes via specific associations with each other and with distinct integrins. Here, we reveal the presence of tetraspanin-enriched microdomains (TEMs) containing the tetraspanins CD9, CD63, CD81, and CD82 at the plasma membrane. Fluorescence and immunoelectron microscopic analyses document that the surface of HeLa cells is covered by several hundred TEMs, each extending over a few hundred nanometers and containing predominantly two or more tetraspanins. Further, we reveal that the human immunodeficiency virus type 1 (HIV-1) Gag protein, which directs viral assembly and release, accumulates at surface TEMs together with the HIV-1 envelope glycoprotein. TSG101 and VPS28, components of the mammalian ESCRT1 (endosomal sorting complex required for transport), which is part of the cellular extravesiculation machinery critical for HIV-1 budding, are also recruited to cell surface TEMs upon virus expression, suggesting that HIV-1 egress can be gated through these newly mapped microdomains.
Nydegger
Sascha
S
Graduate Program in Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA.
Khurana
Sandhya
S
Krementsov
Dimitry N
DN
Foti
Michelangelo
M
Thali
Markus
M
D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism / Q000821:virology; D015686:Gene Products, env / Q000378:metabolism; D015683:Gene Products, gag / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D051861:Kangai-1 Protein / Q000737:chemistry / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism* / Q000821:virology; D008565:Membrane Proteins / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism; D013499:Surface Properties; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology; D060225:Tetraspanin 28; D060245:Tetraspanin 29; D060149:Tetraspanin 30
D015703:Antigens, CD; C554586:CD63 protein, human; C554798:CD81 protein, human; C554869:CD9 protein, human; D015686:Gene Products, env; D015683:Gene Products, gag; D051861:Kangai-1 Protein; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010980:Platelet Membrane Glycoproteins; D060225:Tetraspanin 28; D060245:Tetraspanin 29; D060149:Tetraspanin 30