The membrane-proximal intracytoplasmic tyrosine residue of HIV-1 envelope glycoprotein is critical for basolateral targeting of viral budding in MDCK cells
Open Access
- 15 February 1997
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 16 (4), 695-705
- https://doi.org/10.1093/emboj/16.4.695
Abstract
Budding of retroviruses from polarized epithelial Madin–Darby canine kidney cells (MDCK) takes place specifically at the basolateral membrane surface. This sorting event is suspected to require a specific signal harbored by the viral envelope glycoprotein and it was previously shown that, as for most basolateral proteins, the intracytoplasmic domain plays a crucial role in this targeting phenomenon. It is well known that tyrosine‐based motifs are a central element in basolateral targeting signals. In the present study, site‐directed mutagenesis was used to generate conservative or non‐conservative substitutions of each four intracytoplasmic tyrosines of the human immunodeficiency virus (HIV‐1) envelope glycoprotein. This approach revealed that the membrane‐proximal tyrosine is essential to ensure both the basolateral localization of envelope glycoprotein and the basolateral targeting of HIV‐1 virions. Substitutions of the membrane‐proximal tyrosine did not appear to affect incorporation of envelope glycoprotein into the virions, as assayed by virion infectivity and protein content, nor its capability to ensure its role in viral infection, as determined by viral multiplication kinetics. Altogether, these results indicate that the intracytoplasmic domain of the HIV‐1 envelope glycoprotein harbors a unique, tyrosine‐based, basolateral targeting signal. Such a tyrosine‐based targeting signal may play a fundamental role in HIV transmission and pathogenesis.This publication has 49 references indexed in Scilit:
- Interaction of Tyrosine-Based Sorting Signals with Clathrin-Associated ProteinsScience, 1995
- Ultrastructural Evidence of an Interaction between Env and Gag Proteins during Assembly of HIV Type 1AIDS Research and Human Retroviruses, 1995
- Nef induces CD4 endocytosis: Requirement for a critical dileucine motif in the membrane-proximal CD4 cytoplasmic domainCell, 1994
- Mutational and secondary structural analysis of the basolateral sorting signal of the polymeric immunoglobulin receptor.The Journal of cell biology, 1993
- Signal-Dependent Membrane Protein Trafficking in the Endocytic PathwayAnnual Review of Cell and Developmental Biology, 1993
- Basolateral sorting of LDL receptor in MDCK cells: The cytoplasmic domain contains two tyrosine-dependent targeting determinantsCell, 1992
- Selective membrane protein trafficking: vectorial flow and filterTrends in Biochemical Sciences, 1992
- Basolateral sorting in MDCK cells requires a distinct cytoplasmic domain determinantCell, 1991
- Integral and peripheral protein composition of the apical and basolateral membrane domains in MDCK cellsThe Journal of Membrane Biology, 1989
- Assembly of enveloped viruses in Madin-Darby canine kidney cells: polarized budding from single attached cells and from clusters of cells in suspension.The Journal of cell biology, 1983