Interaction of endocytic signals from the HIV-1 envelope glycoprotein complex with members of the adaptor medium chain family.
The envelope glycoprotein (Env) complex of HIV-1 undergoes rapid internalization from the plasma membrane of human cells by virtue of a tyrosine-based endocytic signal (RQGYSPL, residues 704-710) in the cytosolic tail of the protein (J. F. Rowell et al., J. Immunol. 155, 473-488, 1995). Here we demonstrate that this tyrosine-based signal interacts with the mu 2 (medium) chain of the AP-2 clathrin-associated adaptor, a protein complex involved in endocytosis of cell surface receptors. The same signal is also capable of interacting with two other members of the adaptor medium chain family, mu 1 and mu 3A, which are components of the AP-1 and AP-3 adaptor complexes, respectively. Interactions with mu 1 and mu 3A might be responsible for the targeting of the internalized envelope glycoprotein to lysosomes or to the basolateral plasma membrane of polarized epithelial cells. A second potential tyrosine-based signal (LFSYHRL, residues 760-766) also interacts with mu 1, mu 2, and mu 3A, although it is less important for internalization in vivo probably due to its position within the cytosolic tail. Overexpression of chimeric proteins having the HIV-1 Env cytosolic tail increases expression of the transferrin receptor on the cell surface, probably due to saturation of the cellular pool of mu 2 by the overexpressed proteins. These observations suggest that HIV-1 Env utilizes the protein sorting machinery of the host cells for internalization and sorting at various steps of the endocytic and biosynthetic pathways.
Ohno
H
H
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Aguilar
R C
RC
Fournier
M C
MC
Hennecke
S
S
Cosson
P
P
Bonifacino
J S
JS
D033942:Adaptor Proteins, Vesicular Transport; D030161:Avian Proteins; D002462:Cell Membrane / Q000378:metabolism / Q000821:virology; D002966:Clathrin; D003600:Cytosol / Q000378:metabolism / Q000821:virology; D015870:Gene Expression; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015700:HIV Envelope Protein gp41 / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D034041:Monomeric Clathrin Assembly Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D015728:Receptors, HIV / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D033942:Adaptor Proteins, Vesicular Transport; D030161:Avian Proteins; D002966:Clathrin; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D008562:Membrane Glycoproteins; D034041:Monomeric Clathrin Assembly Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D015728:Receptors, HIV; D011990:Receptors, Transferrin; D011993:Recombinant Fusion Proteins; C439023:clathrin assembly protein AP180; C088981:estrogen-inducible transferrin receptor-like membrane glycoprotein, chicken