RRC ID |
69800
|
著者 |
Rawat SS, Zimmerman C, Johnson BT, Cho E, Lockett SJ, Blumenthal R, Puri A.
|
タイトル |
Restricted lateral mobility of plasma membrane CD4 impairs HIV-1 envelope glycoprotein mediated fusion.
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ジャーナル |
Mol Membr Biol
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Abstract |
We investigated the effect of receptor mobility on HIV-1 envelope glycoprotein (Env)-triggered fusion using B16 mouse melanoma cells that are engineered to express CD4 and CXCR4 or CCR5. These engineered cells are resistant to fusion mediated CD4-dependent HIV-1 envelope glycoprotein. Receptor mobility was measured by fluorescence recovery after photobleaching (FRAP) using either fluorescently-labeled antibodies or transient expression of GFP-tagged receptors in the cells. No significant differences between B16 and NIH3T3 (fusion-permissive) cells were seen in lateral mobility of CCR5 or lipid probes. By contrast CD4 mobility in B16 cells was about seven-fold reduced compared to its mobility in fusion-permissive NIH3T3 cells. However, a CD4 mutant (RA5) that localizes to non-raft membrane microdomains exhibited a three-fold increased mobility in B16 cells as compared with WT-CD4. Interestingly, the B16 cells expressing the RA5 mutant (but not the wild type CD4) and coreceptors supported HIV-1 Env-mediated fusion. Our data demonstrate that the lateral mobility of CD4 is an important determinant of HIV-1 fusion/entry.
|
巻・号 |
25(1)
|
ページ |
83-94
|
公開日 |
2008-1-1
|
DOI |
10.1080/09687680701613713
|
PII |
783706423
|
PMID |
18097956
|
PMC |
PMC3466082
|
MeSH |
Animals
CD4 Antigens / genetics
CD4 Antigens / metabolism*
Gene Products, env / genetics
Gene Products, env / metabolism*
HIV-1 / physiology*
HeLa Cells
Humans
Membrane Fluidity / physiology*
Mice
Mutation
NIH 3T3 Cells
Receptors, CCR5 / genetics
Receptors, CCR5 / metabolism
Receptors, CXCR4 / genetics
Receptors, CXCR4 / metabolism
Virus Internalization*
|
リソース情報 |
ヒト・動物細胞 |
GM95(RCB1026) |