Interactions of the cytoplasmic domains of human and simian retroviral transmembrane proteins with components of the clathrin adaptor complexes modulate intracellular and cell surface expression of envelope glycoproteins
Interactions of the cytoplasmic domains of human and simian retroviral transmembrane proteins with components of the clathrin adaptor complexes modulate intracellular and cell surface expression of envelope glycoproteins
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DOI：
10.1128/jvi.73.2.1350-1361.1999
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发表时间：
1999-02-01
影响因子：
5.4
通讯作者：
Benarous, R
中科院分区：
文献类型：
--
作者：
Berlioz-Torrent, C;Shacklett, BL;Benarous, R
大多数逆转录病毒的跨膜（TM）包膜蛋白（TM-CD）的胞质结构域在其膜近端区域具有基于Tyr的基序，YXX空集。该信号通过网格蛋白相关的AP-1和AP-2接头复合物参与膜受体的运输和内吞。我们使用CD 8-TM-CD嵌合体研究了人类免疫缺陷病毒1型（HIV-1）、猿猴免疫缺陷病毒（SIV）和人类T-白血病病毒1型（HTLV-1）TM-CD的Tyr基序在包膜糖蛋白细胞表面表达中的作用。流式细胞术和共聚焦显微镜研究表明，该基序是CD 8-HTLV嵌合体的细胞表面表达的主要决定因素。YXX空集基序在慢病毒RN-I和SIV包膜的亚细胞分布中也起关键作用。然而，这些编码具有长胞质结构域的TM蛋白的病毒在YXX空集基序的远端具有参与调节细胞表面表达的额外决定簇。我们还使用酵母双杂交系统和体外结合试验证明，所有三种逆转录病毒YXX空集基序与AP复合物的mu 1和mu 2亚基相互作用，HIV-1和SIV TM蛋白的C-末端区域与β 2适应素亚基相互作用。HTLV-I、HIV-1和SIV的TM-CD也与整个AP复合物相互作用。这些结果清楚地表明，逆转录病毒包膜糖蛋白的细胞表面表达是由与接头复合物的相互作用。基于YXX空集的信号是HTLV-1 TM这种相互作用的主要决定因素，HTLV-1 TM含有一个短的胞质结构域，而慢病毒HIV-1和SIV在该信号远端也有其他决定因素。
The cytoplasmic domains of the transmembrane (TM) envelope proteins (TM-CDs) of most retroviruses have a Tyr-based motif, YXXempty set, in their membrane-proximal regions. This signal is involved in the trafficking and endocytosis of membrane receptors via clathrin-associated AP-1 and AP-2 adaptor complexes. We have used CD8-TM-CD chimeras to investigate the role of the Tyr-based motif of human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus (SIV), and human T-leukemia virus type 1 (HTLV-1) TM-CDs in the cell surface expression of the envelope glycoprotein. Flow cytometry and confocal microscopy studies showed that this motif is a major determinant of the cell surface expression of the CD8-HTLV chimera. The YXXempty set motif also plays a key role in subcellular distribution of the envelope of lentiviruses RN-I and SIV, However, these viruses, which encode TM proteins with a long cytoplasmic domain, have additional determinants distal to the YXXempty set motif that participate in regulating cell surface expression. We have also used the yeast two-hybrid system and in vitro binding assays to demonstrate that all three retroviral YXXempty set motifs interact with the mu 1 and mu 2 subunits of AP complexes and that the C-terminal regions of HIV-1 and SIV TM proteins interact with the beta 2 adaptin subunit. The TM-CDs of HTLV-I, HIV-1, and SIV also interact with the whole AP complexes. These results clearly demonstrate that the cell surface expression of retroviral envelope glycoproteins is governed by interactions with adaptor complexes. The YXXempty set-based signal is the major determinant of this interaction for the HTLV-1 TM, which contains a short cytoplasmic domain, whereas the lentiviruses HIV-1 and SIV have additional determinants distal to this signal that are also involved.