Restricted lateral mobility of plasma membrane CD4 impairs HIV-1 envelope glycoprotein mediated fusion

@article{citeulike:2602749, 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.}, author = {Rawat, Satinder S. and Zimmerman, Christina and Johnson, Benitra T. and Cho, Edward and Lockett, Stephen J. and Blumenthal, Robert and Puri, Anu }, citeulike-article-id = {2602749}, doi = {10.1080/09687680701613713}, journal = {Molecular Membrane Biology}, keywords = {envelope, fusion, hiv, raft, receptor}, number = {1}, pages = {83--94}, posted-at = {2008-03-27 17:25:55}, priority = {2}, publisher = {Informa Healthcare}, title = {Restricted lateral mobility of plasma membrane CD4 impairs HIV-1 envelope glycoprotein mediated fusion}, url = {http://dx.doi.org/10.1080/09687680701613713}, volume = {25}, year = {2008} }

TY - JOUR ID - citeulike:2602749 L3 - citeulike-article-id:2602749 TI - Restricted lateral mobility of plasma membrane CD4 impairs HIV-1 envelope glycoprotein mediated fusion JF - Molecular Membrane Biology VL - 25 IS - 1 SP - 83 EP - 94 PB - Informa Healthcare N2 - 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. KW - envelope KW - fusion KW - hiv KW - raft KW - receptor AU - Rawat, Satinder AU - Zimmerman, Christina AU - Johnson, Benitra AU - Cho, Edward AU - Lockett, Stephen AU - Blumenthal, Robert AU - Puri, Anu PY - 2008/// UR - http://dx.doi.org/10.1080/09687680701613713 ER -