Nat.Cell.Bio：HIV-1感染靶细胞的新分子机制被发现

生物谷

生物谷报道：HIV-1病毒的感染需要其外膜糖蛋白gp120诱导CD4和复合受体（CCR5或CXCR4）在细胞表面簇集，这些表面受体的簇集激活了gp41，从而形成复合物以介导病毒包膜和靶细胞的结合。动力学研究发现，这些病毒受体是通过主动运输的方式被转运到包膜和受体的结合位点，这一过程有赖于细胞膜和肌动蛋白骨架的作用，但是HIV-1病毒是如何介导靶细胞的肌动蛋白重排的，其机制并不清楚。

最近，研究人员发现CD4及其复合受体是通过与肌动蛋白结合蛋白丝蛋白-A的相互作用簇集到靶细胞表面的。丝蛋白-A做为一种衔接蛋白，将HIV-1的受体连接到肌动蛋白细胞骨架上，并介导其重排，从而使病毒的感染变得更加容易。这一发现发表在最新一期的《自然-细胞生物学》杂志上。

Figure 1. Identification of filamin-A as a CD4-binding protein.
(a) Growth and -galactosidase activity of yeast colonies cotransfected with the indicated plasmids on -LW and -LHAW selection plates after 72 h; blue indicates specific interaction of the two proteins. FLNa, filamin-A. (b) Pulldown of in vitro-translated, biotin-labelled filamin-A (residues 968–1252) interaction with GST–CD4^IC or GST, analysed by immunoblot. A fraction of the non-retained material (not bound), the first wash step and eluted proteins (bound) are shown. (c) GST or GST–CD4^IC were incubated with total cell extracts and pulldown performed. Immunoblot of GST-bound proteins and cell extracts (input) using anti-filamin-A antibody (top) and Coomassie blue staining of the gel (bottom). (d) Immunoisolation of CD4 with anti-CD4-coated magnetic beads after nitrogen cavitation of cells. Affinity-isolated membranes (left) and cell lysates (right) were blotted with indicated antibodies. (e) MT-2 cells were incubated with an activating anti-CD4 antibody, immunoprecipitated with anti-CD4 or IgG and SDS–PAGE-resolved CD4-bound proteins were blotted sequentially with the indicated antibodies. (f) Membrane proteins immunoprecipitated (IP) with control IgG or anti-filamin-A antibodies were blotted for CD4 and filamin-A. (g) Coredistribution of endogenous CD4 and filamin-A. Jurkat cells were incubated with IgG- or anti-CD4-coated beads, fixed and stained with anti-filamin-A antibody (red). Merge of transmission and red fluorescence images is shown. Representative cells are shown from more than 30 cells recorded in two experiments. The scale bars represent 10 m.

原文出处：

Nature Cell Biology

Filamin-A regulates actin-dependent clustering of HIV receptors
Sonia Jiménez-Baranda, Concepción Gómez-Moutón, Ana Rojas, Lorena Martínez-Prats, Emilia Mira, Rosa Ana Lacalle, Alfonso Valencia, Dimiter S. Dimitrov, Antonella Viola, Rafael Delgado, Carlos Martínez-A. & Santos Mañes
Published online: 17 June 2007 | doi:10.1038/ncb1610
Abstract | Full text | PDF (1,413K) | Supplementary Information

相关基因：

NEWENTRY

Record to support submission of GeneRIFs for a gene not in Entrez Gene (Human immundeficiency virus type 1; Human immunodeficiencey virus type 1; Human immunodeficiency virus type 1; human immunodeficiency virus 1 HIV-1; human immunodeficiency virus HIV-1; human immunodeficiency virus type 1 ,HIV-1; human immunodeficiency virus type 1 HIV 1; human immunodeficiency virus type 1 HIV-1; human immunodeficiency virus type 1 HIV1; human immunodeficiency virus type 1, HIV-1; human immunodeficiency virus type I HIV-1; human immunodeficiency virus type-1 HIV-1; human immunodeficiency virus-1 HIV-1). [Human immunodeficiency virus 1]
GeneID: 2828719